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Diabetes Mellitus

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance metabolism by insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin. Type 1 Type 1 Spinal Muscular Atrophy DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy and the resulting lack of insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin. Type 2 Type 2 Spinal Muscular Atrophy DM has a significant association with obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity and is characterized by insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing, as well as relative insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin deficiency. Genetically determined causes of diabetes (e.g., maturity-onset diabetes of the young and late autoimmune diabetes in adults) are being increasingly recognized, but they make up a small portion of cases. There is no definitive cure for DM. The objective of management is the prevention of complications, which may include coronary artery disease Coronary artery disease Pathological processes of coronary arteries that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause. Stable and Unstable Angina, CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease, retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome, and neuropathy Neuropathy Leprosy. Long-term monitoring and maintenance of optimal blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance levels are key to preventing complications. Treatment is specific to the type of diabetes, with glycemic control as the goal in all types; insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin replacement is essential in type 1 Type 1 Spinal Muscular Atrophy, and a healthy diet, lifestyle changes, and medications are important in type 2 Type 2 Spinal Muscular Atrophy.

Last updated: Jun 9, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Definition

Diabetes mellitus (DM) is a disorder of carbohydrate metabolism. Diabetes mellitus usually occurs in genetically predisposed individuals and is characterized by inadequate production of insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin or resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin’s action on the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy. These features result in hyperglycemia and the long-term pathologic sequelae of DM.

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Epidemiology

Type 1 Type 1 Spinal Muscular Atrophy

  • Nearly 1.6 million people in the United States affected in 2018
  • Typically presents in children or adults < 25 years of age
  • 5%–10% of all diabetics
  • Has a strong age, race, and geographic bias Bias Epidemiological studies are designed to evaluate a hypothesized relationship between an exposure and an outcome; however, the existence and/or magnitude of these relationships may be erroneously affected by the design and execution of the study itself or by conscious or unconscious errors perpetrated by the investigators or the subjects. These systematic errors are called biases. Types of Biases:
    • Most commonly diagnosed at ages 4–6 years, with 2nd peak in early teenage years
    • Highest geographic density in Finland and Sardinia
    • In the United States, predominantly seen in non-Hispanic White children and adolescents
  • Genetic predisposition

Type 2 Type 2 Spinal Muscular Atrophy

  • In 2017, estimated worldwide prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency was 425 million people
  • Usually presents at ages > 40 years but can be earlier
  • 90%–95% of diabetics
  • Estimated prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency 10.5% in the United States (and 27% in Americans > 65 years)
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency much higher in Native Americans, Blacks, Hispanics, Asian Americans, and Pacific Islanders

Gestational diabetes

  • Occurs in 5%–7% of pregnancies in the United States
  • Ethnic and geographic prevalences mirror those of type 2 Type 2 Spinal Muscular Atrophy DM
  • In the United States, elevated prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency in African American, Hispanic American, Native American, Pacific Islander, and South or East Asian women
  • Increased incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of nongestational diabetes later in life

Risk factors:

  • Hemoglobin A1c ≥ 5.7% or elevated fasting glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance level prior to pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Gestational diabetes in previous pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • ≥ 110% of ideal body weight or BMI BMI An indicator of body density as determined by the relationship of body weight to body height. Bmi=weight (kg)/height squared (m2). Bmi correlates with body fat (adipose tissue). Their relationship varies with age and gender. For adults, bmi falls into these categories: below 18. 5 (underweight); 18. 5-24. 9 (normal); 25. 0-29. 9 (overweight); 30. 0 and above (obese). Obesity (weight in kilograms divided by square of the height in meters) > 30 during gestation
  • Gaining excessive weight during 1st half of gestation
  • Family history Family History Adult Health Maintenance of DM
  • Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance in urine at 1st prenatal visit
  • Previous children ≥ 4 kg at birth 
  • Abnormal lipid studies
  • Polycystic ovary syndrome ( PCOS PCOS Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%-10% of women in the age group. It is characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction. Polycystic Ovarian Syndrome)
  • Use of glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids
  • Multiple (twin, triplet, etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC).) gestation

Late Autoimmune Diabetes in Adults (LADA)

Maturity Onset Diabetes of the Young (MODY)

  • Affects 1%–5% of all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with diabetes mellitus
  • No reported ethnic predilection

Etiology

Type 1 Type 1 Spinal Muscular Atrophy

  • Autoimmune destruction of pancreatic β cells by glutamic acid Glutamic acid A non-essential amino acid naturally occurring in the l-form. Glutamic acid is the most common excitatory neurotransmitter in the central nervous system. Urea Cycle decarboxylase ( GAD GAD Generalized anxiety disorder (GAD) is a common mental condition defined by excessive, uncontrollable worrying causing distress and occurring frequently for at least 6 months. Generalized anxiety disorder is more common in women. Clinical presentation includes fatigue, low concentration, restlessness, irritability, and sleep disturbance. Generalized Anxiety Disorder) antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions leading to insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin deficiency
  • HLA-linked (HLA-DQ, HLA-DR3, and HLA-DR4 HLA-DR4 Goodpasture Syndrome
  • Associated with other autoimmune conditions

Type 2 Type 2 Spinal Muscular Atrophy

  • Caused by insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing 
  • Relative insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin deficiency
  • Strong family history Family History Adult Health Maintenance/genetic component

Gestational diabetes

  • Unclear etiology, but not autoimmune
  • Increased insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin secretion Secretion Coagulation Studies but not sufficient to maintain normal glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance levels
  • Decreased insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin sensitivity

Late autoimmune diabetes in adults

  • Similar to type 1 Type 1 Spinal Muscular Atrophy diabetes, LADA is closely linked to genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure in the HLA complex
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity and other factors that cause insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing

Maturity onset diabetes of the young

  • Autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance inheritance
  • 14 distinct subtypes 
  • Mechanisms involved:
    • Defective transcriptional regulation
    • Abnormal metabolic enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
    • Protein misfolding
    • Dysfunctional ion channels Channels The Cell: Cell Membrane
    • Impaired signal transduction Transduction The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a gene transfer technique. Bacteriology

Pathophysiology

Type 1 Type 1 Spinal Muscular Atrophy

  • T-cell immune-mediated destruction of insulin-producing pancreatic islet cells
  • Autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques (not always detectable):
    • GAD GAD Generalized anxiety disorder (GAD) is a common mental condition defined by excessive, uncontrollable worrying causing distress and occurring frequently for at least 6 months. Generalized anxiety disorder is more common in women. Clinical presentation includes fatigue, low concentration, restlessness, irritability, and sleep disturbance. Generalized Anxiety Disorder autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques:
      • Target insulin-producing pancreatic β cells 
      • Autoimmune destruction of 80%–90% of cells
      • Leads to insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin deficiency and hyperglycemia.
    • Islet cell Islet cell Pancreatic Neuroendocrine Tumors (PanNETs) cytoplasmic autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques (ICA)
    • Insulinoma-associated-2 (IA-2) autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques 
    • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques (IAAs)
    • Zinc Zinc A metallic element of atomic number 30 and atomic weight 65. 38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with anemia, short stature, hypogonadism, impaired wound healing, and geophagia. It is known by the symbol zn. Trace Elements transporter-8 autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques (ZnT8A)
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have minimal to no autonomous insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin production:
    • Require insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin replacement at all times to treat hyperglycemia 
    • Failure to supplement insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin leads to:
      • Diabetic ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis ( DKA DKA Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency. Hyperglycemic Crises) (can be life-threatening)
      • Chronic complications of diabetes

Type 2 Type 2 Spinal Muscular Atrophy

Type 2 Type 2 Spinal Muscular Atrophy DM is a combination of defective insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin secretion Secretion Coagulation Studies and decreased insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin sensitivity.

  • Defective insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin secretion Secretion Coagulation Studies:
    • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin secretion Secretion Coagulation Studies by β cells requires glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance transport into the cell
    • Mediated by glucose transporter 2 Glucose transporter 2 A glucose transport facilitator that is expressed primarily in pancreatic beta cells; liver; and kidneys. It may function as a glucose sensor to regulate insulin release and glucose homeostasis. Digestion and Absorption of Carbohydrates (GLUT-2)
    • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity and high-fat diet may affect Affect The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves. Psychiatric Assessment this transport, causing decreased insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin secretion Secretion Coagulation Studies
  • Peripheral insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing:
    • With constant high intake of glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance, there is a constant high demand for insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin
    • Hyperinsulinemia leads to decrease in sensitivity of the insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, muscle, and adipose cells Adipose Cells Fat Necrosis of the Breast.
    • Down-regulation Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (gene expression regulation), mRNAs, and proteins. Pharmacokinetics and Pharmacodynamics of receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors leads to vicious cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation of high insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin levels.
  • Additional mechanisms:
    • Impaired hepatic sensitivity to insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin leads to lack of inhibition of glycogenolysis Glycogenolysis The release of glucose from glycogen by glycogen phosphorylase (phosphorolysis). The released glucose-1-phosphate is then converted to glucose-6-phosphate by phosphoglucomutase before entering glycolysis. Glycogenolysis is stimulated by glucagon or epinephrine via the activation of phosphorylase kinase. Glycogen Metabolism and gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis
    • Hyperglycemia can impair pancreatic β-cell function and exacerbate insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing.
    • High demand for insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin and excessive production of pancreatic enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes causes pro-amylin accumulation and pancreatic apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage.
    • Progressive pancreatic β-cell failure

There are several effects of chronic hyperglycemia:

  • High serum glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance level (> 180 mg/dL) exceeds renal threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction causing:
    • Glucosuria
    • Increase in osmotic pressure Osmotic pressure The pressure required to prevent the passage of solvent through a semipermeable membrane that separates a pure solvent from a solution of the solvent and solute or that separates different concentrations of a solution. It is proportional to the osmolality of the solution. Intravenous Fluids of the urine leading to polyuria Polyuria Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. Renal Potassium Regulation
    • Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration leading to polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus
  • Intracellular glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance deficiency, causing polyphagia
  • Chronic complications of diabetes

Gestational diabetes

  • β-cell dysfunction in setting of insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing (similar to type 2 Type 2 Spinal Muscular Atrophy)
  • Defect is thought to exist prior to conception; stress from pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care unmasks and worsens it.
  • Effects of maternal hyperglycemia on pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care:
    • Increased risk for preeclampsia Preeclampsia A complication of pregnancy, characterized by a complex of symptoms including maternal hypertension and proteinuria with or without pathological edema. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Hypertensive Pregnancy Disorders
    • Increased risk for birth complicated by shoulder dystocia Shoulder Dystocia Obstetric complication during obstetric delivery in which exit of the fetus is delayed due to physical obstruction involving fetal shoulder(s). Complications during Childbirth 
  • Effects of maternal hyperglycemia on developing fetus: 
    • Increased risk for postnatal hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia 
    • Increased risk for large-for-gestational-age fetus

Late autoimmune diabetes in adults

  • Autoimmune process (similar to type 1 Type 1 Spinal Muscular Atrophy)
  • Autoantibody-mediated destruction of β cells (particularly GAD GAD Generalized anxiety disorder (GAD) is a common mental condition defined by excessive, uncontrollable worrying causing distress and occurring frequently for at least 6 months. Generalized anxiety disorder is more common in women. Clinical presentation includes fatigue, low concentration, restlessness, irritability, and sleep disturbance. Generalized Anxiety Disorder)
  • Slow, progressive process 
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship often not insulin-dependent at presentation
    • Oral medication rapidly loses effect
    • Eventually leads to insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin requirement 

Maturity onset diabetes of the young

  • Genetic defects leading to impaired glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance sensing and insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin secretion Secretion Coagulation Studies
  • Mutations in hepatocyte nuclear factor-4-alpha (HNF4A) cause 10% of cases of MODY.
Pancreas

Pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy:
Pancreatic exocrine function involves the acinar cells Acinar cells Cells lining the saclike dilatations known as acini of various glands or the lungs. Gastrointestinal Secretions secreting digestive enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes that are transported into the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy by the pancreatic duct. The endocrine function of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy involves the secretion Secretion Coagulation Studies of insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin (produced by beta cells) and glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions (produced by alpha cells) within the pancreatic islets. These 2 hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types regulate the rate of glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance metabolism in the body. The photomicrograph shows pancreatic islets.

Image: “ Pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy” by Regents of University of Michigan Medical School. License: CC By 4.0

Clinical Presentation

Type 1 Type 1 Spinal Muscular Atrophy

DKA DKA Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency. Hyperglycemic Crises:

Type 1 Type 1 Spinal Muscular Atrophy DM often presents urgently with DKA DKA Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency. Hyperglycemic Crises:

  • Usually precipitated by a “tipping” event (e.g., viral illness, trauma, emotional stress)
  • Depressed mental status
  • Abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Fruity “ acetone Acetone A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. Ketone Body Metabolism” breath

Hyperglycemia:

Type 1 Type 1 Spinal Muscular Atrophy DM can also present with classic symptoms of hyperglycemia:

  • Polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus
  • Polyphagia
  • Polyuria Polyuria Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. Renal Potassium Regulation (can present as enuresis Enuresis Involuntary discharge of urine after expected age of completed development of urinary control. This can happen during the daytime (diurnal enuresis) while one is awake or during sleep (nocturnal enuresis). Enuresis can be in children or in adults (as persistent primary enuresis and secondary adult-onset enuresis). Elimination Disorders and nocturia Nocturia Frequent urination at night that interrupts sleep. It is often associated with outflow obstruction, diabetes mellitus, or bladder inflammation (cystitis). Diabetes Insipidus in children)
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Blurred vision Blurred Vision Retinal Detachment 

Type 2 Type 2 Spinal Muscular Atrophy

Type 2 Type 2 Spinal Muscular Atrophy DM has a gradual onset, initially remaining asymptomatic for several years:

  • High glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance levels often detected on screening tests Screening tests Screening tests are used to identify people in the early stages of a disease and enable early intervention with the goal of reducing morbidity and mortality. Epidemiological Values of Diagnostic Tests before symptoms appear
  • Can present with classic symptoms of hyperglycemia, as in type 1 Type 1 Spinal Muscular Atrophy DM
  • Sometimes diagnosed with hyperosmolar hyperglycemic state Hyperosmolar hyperglycemic state A serious complication of type 2 diabetes mellitus. It is characterized by extreme hyperglycemia; dehydration; serum hyperosmolarity; and depressed consciousness leading to coma in the absence of ketosis and acidosis. Hyperglycemic Crises or signs of long-term complications before the diagnosis is known
  • Rarely, DKA DKA Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency. Hyperglycemic Crises present
  • Nonspecific symptoms due to hyperglycemia: 
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions manifestations: 
    • Recurrent cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis or fungal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • Poor or delayed wound healing Wound healing Wound healing is a physiological process involving tissue repair in response to injury. It involves a complex interaction of various cell types, cytokines, and inflammatory mediators. Wound healing stages include hemostasis, inflammation, granulation, and remodeling. Wound Healing
    • Generalized pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema)
    • Acanthosis nigricans: hyperpigmented velvet-like plaques on the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions of the axilla Axilla The axilla is a pyramid-shaped space located between the upper thorax and the arm. The axilla has a base, an apex, and 4 walls (anterior, medial, lateral, posterior). The base of the pyramid is made up of the axillary skin. The apex is the axillary inlet, located between the 1st rib, superior border of the scapula, and clavicle. Axilla and Brachial Plexus: Anatomy or neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess or between the digits

Gestational diabetes

Late autoimmune diabetes in adults

Maturity onset diabetes of the young

  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present at young age, not usually obese: often misdiagnosed as type 1 Type 1 Spinal Muscular Atrophy
  • Not insulin-resistant:
    • Distinguishing from type 2 Type 2 Spinal Muscular Atrophy can be challenging
    • Characteristic symptoms of insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing (e.g., acanthosis nigricans) often absent

Diagnosis

Diagnosis of diabetes is based on the presence of inappropriate hyperglycemia in the context of suspicious clinical symptoms.

Table: Diagnostic criteria for diabetes mellitus
Test Normal range Increasd risk for diabetes (prediabetes) Diabetes
Random plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance Classic hyperglycemic symptoms plus a random plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance > 200 mg/dL
Fasting plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance
(fasting 8 hours)
< 100 mg/dL 100–125 mg/dL > 126 mg/dL
Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance after a 2-hour,
75-g OGTT
< 140 mg/dL 140–199 mg/dL ≥ 200 mg/dL

Hemoglobin A1c < 5.7% 5.7%–6.4% ≥ 6.5%
OGTT: oral glucose-tolerance test

Type 1 Type 1 Spinal Muscular Atrophy

  • Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children may show microalbuminuria, glucosuria, or ketone bodies Ketone bodies The metabolic substances acetone; 3-hydroxybutyric acid; and acetoacetic acid (acetoacetates). They are produced in the liver and kidney during fatty acids oxidation and used as a source of energy by the heart, muscle and brain. Ketone Body Metabolism 
  • DM-related autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques (anti-GAD65, ICA, anti-IA-2)
  • C-peptide
    • Low levels indicate insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin deficiency ( type 1 Type 1 Spinal Muscular Atrophy DM)
    • High levels indicate insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing ( type 2 Type 2 Spinal Muscular Atrophy DM)

Type 2 Type 2 Spinal Muscular Atrophy

  • Screening Screening Preoperative Care recommended for:
    • Individuals > 45 years without risk factors
    • Individuals 35–70 years who are overweight or obese
    • Younger if risk factors present
    • Potential considerations for screening Screening Preoperative Care:
      • Women with a history of gestational diabetes
      • Individuals starting antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs for HIV HIV Anti-HIV Drugs
      • 1st degree relative with diabetes
  • Diagnostic criteria: (any 1 of the following)
    • Fasting (> 8 hours) plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance ≥ 126 mg/dL (prediabetes, 100–125)
    • Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance ≥ 200 mg/dL 2 hours after ingestion of 75 g of glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance (oral glucose-tolerance test (OGTT)) (prediabetes, 140–199)
    • Hemoglobin A1c (HbA1c) ≥ 6.5% (prediabetes, 5.7–6.4)
    • Random plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance ≥ 200 mg/dL in a patient with classic symptoms 

Gestational diabetes

Oral glucose-tolerance test is recommended during the 24th–28th week of pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care. Abnormal results are:

  • Fasting glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance: ≥ 92 mg/dL
  • 1-hour glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance: ≥ 180 mg/dL 
  • 2-hour glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance: ≥ 153 mg/dL

Late autoimmune diabetes in adults

  • Same diagnostic criteria as for type 2 Type 2 Spinal Muscular Atrophy DM
  • GAD65 antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions positive: helps to identify patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship thought to have type 2 Type 2 Spinal Muscular Atrophy DM, but who will likely require insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin for glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance control

Maturity onset diabetes of the young

  • To differentiate from type 1 Type 1 Spinal Muscular Atrophy: lack serum autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques
  • To differentiate from type 2 Type 2 Spinal Muscular Atrophy:
    • Currently no good biochemical markers
    • Family history Family History Adult Health Maintenance of DM not suggestive
    • Diabetes mellitus in the absence of obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity or secondary markers of insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin sensitivity can be suggestive.
    • Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies

Monitoring

Self-monitoring

  • Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance monitoring:
    • Fasting 
    • Near meals (before and/or after, depending on patient)
    • With symptoms of hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia or hyperglycemia
    • Before important activities (e.g., flying a plane/driving a school bus)
    • New continuous glucose-monitoring systems often used in type 1 Type 1 Spinal Muscular Atrophy DM
  • Regular Regular Insulin foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy hygiene and self-monitoring for skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions ulceration Ulceration Corneal Abrasions, Erosion, and Ulcers 

Clinician Clinician A physician, nurse practitioner, physician assistant, or another health professional who is directly involved in patient care and has a professional relationship with patients. Clinician–Patient Relationship monitoring

  • Regular Regular Insulin weight and BP checks
  • Lab testing of HbA1c levels yearly to evaluate glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance control and efficacy of therapy:
    • HbA1c provides an estimate of patient’s blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance over previous 3 months.
    • Target goal: < 7%
    • Less strict in elderly patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship/children
  • Annual microalbumin : creatinine ratio urine test
  • Lipid testing annually:
  • Annual retinal eye exam 
  • Prophylactic vaccines ( influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza, pneumococcal)
  • Regular Regular Insulin dental exams

Management

No definitive cure exists for diabetes. Management centers around correcting high blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance with insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin ( type 1 Type 1 Spinal Muscular Atrophy) or oral medication ( type 2 Type 2 Spinal Muscular Atrophy), avoiding low blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance, and treating the clinical effects of chronic hyperglycemia.

Multidisciplinary approach

Initial management is with patient education and support.

  • Lifestyle modifications: 
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation to decrease the risk of comorbid complications
  • Stress management
  • Pharmacologic therapies to meet individualized glycemic goals:
    • Choice of medication depends on the level of HbA1c at the time of diagnosis
    • Need to be adjusted with CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease or intolerance

Oral medications

 Classes of oral medications used to treat insulin-resistant diabetes (usually type 2 Type 2 Spinal Muscular Atrophy):

  • Biguanide ( metformin Metformin A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. Non-insulinotropic Diabetes Drugs): 1st-line drug of choice
  • Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance cotransporter-2 (SGLT-2) inhibitors: demonstrated benefit for cardiorenal outcomes, especially for heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) hospitalization Hospitalization The confinement of a patient in a hospital. Delirium, risk of kidney disease progression, and mortality Mortality All deaths reported in a given population. Measures of Health Status
  • Dipeptidyl peptidase-4 Dipeptidyl peptidase-4 A serine protease that catalyses the release of an n-terminal dipeptide. Several biologically-active peptides have been identified as dipeptidyl peptidase 4 substrates including incretins; neuropeptides; and chemokines. The protein is also found bound to adenosine deaminase on the t-cell surface and is believed to play a role in t-cell activation. Angioedema (DPP-4) inhibitors
  • Sulfonylureas Sulfonylureas Sulfonamides and Trimethoprim
  • Thiazolidinediones Thiazolidinediones Thiazoles with two keto oxygens. Members are insulin-sensitizing agents which overcome insulin resistance by activation of the peroxisome proliferator activated receptor gamma (ppar-gamma). Non-insulinotropic Diabetes Drugs

Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin therapy

Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin therapy is used to treat type 1 Type 1 Spinal Muscular Atrophy DM and sometimes type 2 Type 2 Spinal Muscular Atrophy DM when oral medications alone are no longer sufficient.

  • Rapid-acting insulins: start working in 10–15 minutes
    • Glulisine Glulisine Insulin (brand name Apidra)
    • Lispro Lispro Insulin that has been modified so that the b-chain contains a lysine at position 28 instead of a proline and a proline at position 29 instead of a lysine. It is used to manage blood glucose levels in patients with type 2 diabetes. Insulin (brand name Humalog)
    • Aspart Aspart Insulin that has been modified to contain an aspartic acid instead of a proline at position 38 of the b-chain. Insulin (brand name NovoLog)
  • Short-acting insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin
    • Starts working in 30 minutes, peaks at 2–3 hours
    • Rapid-acting and short-acting insulins are used in combination with longer-acting insulins or in insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin pumps for type 1 Type 1 Spinal Muscular Atrophy diabetes
  • Long-acting insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin: last 12–24 hours
    • NPH NPH Normal pressure hydrocephalus (NPH) is a neurodegenerative disorder characterized by the triad of gait abnormalities, dementia, and urinary urgency or incontinence. Normal pressure hydrocephalus can be either idiopathic or secondary to intraventricular or subarachnoid hemorrhage. Normal Pressure Hydrocephalus (generic, stands for neutral protamine Hagedorn Neutral Protamine Hagedorn Insulin)
    • Glargine Glargine A recombinant long acting insulin and hypoglycemic agent that is used to manage blood glucose in patients with diabetes mellitus. Insulin (brand name Lantus or Basaglar)
    • Detemir Detemir A recombinant long-acting insulin and hypoglycemic agent in which a myristic acid is conjugated to a lysine at position b29. It is used to manage blood glucose levels in patients with diabetes mellitus. Insulin (brand name Levemir)

Noninsulin injectable therapies

  • Glucagon-like peptide-1 ( GLP-1 GLP-1 A peptide of 36 or 37 amino acids that is derived from proglucagon and mainly produced by the intestinal l cells. Glp-1(1-37 or 1-36) is further n-terminally truncated resulting in glp-1(7-37) or glp-1-(7-36) which can be amidated. These glp-1 peptides are known to enhance glucose-dependent insulin release, suppress glucagon release and gastric emptying, lower blood glucose, and reduce food intake. Insulinomas) receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors agonists: preferred in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who already have cardiac or renal comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus:
    • Exenatide (brand name Byetta)
    • Dulaglutide (brand name Trulicity)
    • Liraglutide (brand name Victoza)
    • Semaglutide (Ozempic) — also available in tablet form (Rybelsus)
  • Amylin mimetic pramlintide Pramlintide Non-insulinotropic Diabetes Drugs (brand name Symlin) (not often used):
    • Suppresses plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions secretion Secretion Coagulation Studies
    • Slows gastric emptying Gastric emptying The evacuation of food from the stomach into the duodenum. Gastrointestinal Motility
    • Promotes satiety

Special considerations with insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin use

The dawn phenomenon:

  • Early in the morning, the effect of exogenous insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin injected the day before disappears.
  • Insulin-antagonistic hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types increase physiologically in the morning.
  • May cause morning hyperglycemia

The Somogyi effect:

  • Rebound morning hyperglycemia
  • Response to hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia during the night after excessive amounts of exogenous insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin the evening before

Complications

Potential complications

Type 1 Type 1 Spinal Muscular Atrophy:

  • DKA DKA Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency. Hyperglycemic Crises:
    • Severe hyperglycemia
    • Presents with vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, shallow respirations, and confusion
    • Elevation of serum beta-hydroxybutyrate Beta-hydroxybutyrate Butyric acid substituted in the beta or 3 position. It is one of the ketone bodies produced in the liver. Ketone Body Metabolism and urine ketones Ketones Organic compounds containing a carbonyl group =C=O bonded to two hydrocarbon groups. Basics of Carbohydrates is diagnostic.
    • Can lead to coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma and death if untreated
    • Requires hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
  • Severe insulin-induced hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia:
    • Confusion
    • Irritability
    • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
    • Slurred speech Slurred Speech Cerebellar Disorders
    • Diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis
    • Can lead to loss of consciousness, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, or death if untreated
    • Treat with glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions injection or nasal administration.

Type 2 Type 2 Spinal Muscular Atrophy:

  • Hyperosmolar hyperglycemic state Hyperosmolar hyperglycemic state A serious complication of type 2 diabetes mellitus. It is characterized by extreme hyperglycemia; dehydration; serum hyperosmolarity; and depressed consciousness leading to coma in the absence of ketosis and acidosis. Hyperglycemic Crises ( HHS HHS Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Hyperosmolar hyperglycemic state occurs due to a relative deficiency of insulin or insulin resistance, leading to severe hyperglycemia and elevated serum osmolality. Hyperglycemic Crises): 
    • Severe hyperglycemia results in high osmolarity Osmolarity The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Hypernatremia without significant ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis
    • Symptoms include signs of dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration, weakness, leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy cramps Cramps Ion Channel Myopathy, vision Vision Ophthalmic Exam problems, and altered level of consciousness Altered Level of Consciousness Intracerebral Hemorrhage.
    • Requires hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
  • Insulin-associated weight gain and potential causes:
    • Continued dietary indiscretion
    • Reduction in glycosuria Glycosuria The appearance of an abnormally large amount of glucose in the urine, such as more than 500 mg/day in adults. It can be due to hyperglycemia or genetic defects in renal reabsorption (renal glycosuria). Kidney Function Tests with now improved glycemic control
    • Snacking to support an insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin dose that is too high (overtreatment of hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia)
    • Weight gain worsens insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing and may prompt insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin dose escalation, leading to a vicious cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation.

Gestational diabetes:

The risk of complications is proportional to the level of hyperglycemia:

  • Miscarriage Miscarriage Spontaneous abortion, also known as miscarriage, is the loss of a pregnancy before 20 weeks’ gestation. However, the layperson use of the term “abortion” is often intended to refer to induced termination of a pregnancy, whereas “miscarriage” is preferred for spontaneous loss. Spontaneous Abortion
  • Fetal deformities
  • Large-for-gestational-age fetus, often requiring cesarean delivery Cesarean Delivery Cesarean delivery (CD) is the operative delivery of ≥ 1 infants through a surgical incision in the maternal abdomen and uterus. Cesarean deliveries may be indicated for a number of either maternal or fetal reasons, most commonly including fetal intolerance to labor, arrest of labor, a history of prior uterine surgery, fetal malpresentation, and placental abnormalities. Cesarean Delivery
  • Macrosomia
  • Preeclampsia Preeclampsia A complication of pregnancy, characterized by a complex of symptoms including maternal hypertension and proteinuria with or without pathological edema. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Hypertensive Pregnancy Disorders
  • Hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia in the infant

Chronic complications

Both type 1 Type 1 Spinal Muscular Atrophy and type 2 Type 2 Spinal Muscular Atrophy DM can cause diabetic complications.

  • Macrovascular disease: 
    • Coronary heart disease Coronary heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease/acute MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction
    • Cerebrovascular disease/stroke
    • Peripheral artery disease Peripheral artery disease Peripheral artery disease (PAD) is obstruction of the arterial lumen resulting in decreased blood flow to the distal limbs. The disease can be a result of atherosclerosis or thrombosis. Patients may be asymptomatic or have progressive claudication, skin discoloration, ischemic ulcers, or gangrene. Peripheral Artery Disease/claudication
  • Microvascular disease: 
    • CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
    • Diabetic retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome
    • Neuropathy Neuropathy Leprosy/ foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy ulcers
  • Fatty liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease

Related videos

Differential Diagnosis

Type 1 Type 1 Spinal Muscular Atrophy

  • Maturity onset diabetes of the young (MODY): clinically heterogeneous disorder characterized by non-insulin-dependent diabetes diagnosed at a young age (< 25 years) with autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance transmission and lack of autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques.
  • Psychogenic polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus: excessive volitional water intake. Psychogenic polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus is often seen in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with severe mental illness and/or developmental disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment. There may be no physical effects, but hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia can occur.
  • Nephrogenic diabetes insipidus Nephrogenic Diabetes Insipidus Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of DI: central DI (CDI) and nephrogenic DI (NDI). In nephrogenic DI, the kidneys fail to respond to circulating ADH. Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus: form of diabetes insipidus Diabetes Insipidus Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of DI: central DI (CDI) and nephrogenic DI (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus primarily due to kidney pathology. Nephrogenic diabetes insipidus Nephrogenic Diabetes Insipidus Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of DI: central DI (CDI) and nephrogenic DI (NDI). In nephrogenic DI, the kidneys fail to respond to circulating ADH. Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus differs from central/neurogenic diabetes insipidus Diabetes Insipidus Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. There are 2 subforms of DI: central DI (CDI) and nephrogenic DI (NDI). Both conditions result in the kidneys being unable to concentrate urine, leading to polyuria, nocturia, and polydipsia. Diabetes Insipidus, which is caused by insufficient levels of antidiuretic hormone Antidiuretic hormone Antidiuretic hormones released by the neurohypophysis of all vertebrates (structure varies with species) to regulate water balance and osmolarity. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a cystine. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the kidney collecting ducts to increase water reabsorption, increase blood volume and blood pressure. Hypernatremia (ADH).
  • High-output renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome: associated with polyuria Polyuria Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. Renal Potassium Regulation from other causes, including stress, trauma, burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns, or surgery.

Type 2 Type 2 Spinal Muscular Atrophy

  • Metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome: group of conditions including central obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity, high BP, high blood sugar, high serum triglycerides Triglycerides Fatty Acids and Lipids, and low serum HDL.
  • Latent autoimmune diabetes of adulthood (LADA): form of type 1 Type 1 Spinal Muscular Atrophy DM. When the diagnosis is not clear, antibody testing in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with newly manifested diabetes is helpful to establish this diagnosis.
  • Steroid-induced hyperglycemia: Prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants and similar medications may cause significant hyperglycemia. Steroid-induced hyperglycemia may be transient and resolve with completion of the course of steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors, or it may persist and reveal underlying type 2 Type 2 Spinal Muscular Atrophy DM.
  • Secondary diabetes: due to Cushing’s disease, acromegaly Acromegaly A condition caused by prolonged exposure to excessive human growth hormone in adults. It is characterized by bony enlargement of the face; lower jaw (prognathism); hands; feet; head; and thorax. The most common etiology is a growth hormone-secreting pituitary adenoma. Acromegaly and Gigantism, or glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions hypersecretion caused by islet alpha cell tumor Tumor Inflammation, Down syndrome Down syndrome Down syndrome, or trisomy 21, is the most common chromosomal aberration and the most frequent genetic cause of developmental delay. Both boys and girls are affected and have characteristic craniofacial and musculoskeletal features, as well as multiple medical anomalies involving the cardiac, gastrointestinal, ocular, and auditory systems. Down syndrome (Trisomy 21) ( trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 21), or hemochromatosis Hemochromatosis A disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. Hereditary Hemochromatosis, chronic pancreatitis Chronic pancreatitis Chronic pancreatitis is due to persistent inflammation, fibrosis, and irreversible cell damage to the pancreas, resulting in a loss of endocrine and exocrine gland function. The most common etiologies are alcohol abuse and pancreatic duct obstruction. Patients often present with recurrent epigastric abdominal pain, nausea, and features of malabsorption syndrome (diarrhea, steatorrhea, and weight loss). Chronic Pancreatitis, or pancreatic malignancy Malignancy Hemothorax.

References

  1. Levitsky, L.L. (2020). Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents. UpToDate. Retrieved April 15, 2021, from https://www.uptodate.com/contents/epidemiology-presentation-and-diagnosis-of-type-1-diabetes-mellitus-in-children-and-adolescents
  2. Inzucchi, S. (2021). Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults.UpToDate. Retrieved April 15, 2021, from https://www.uptodate.com/contents/clinical-presentation-diagnosis-and-initial-evaluation-of-diabetes-mellitus-in-adults
  3. ADA. (2020). Statistics About Diabetes. Retrieved April 16, 2021, from https://www.diabetes.org/resources/statistics/statistics-about-diabetes#:~:text=Overall%20Numbers%2C%20Diabetes%20and%20Prediabetes.%20Undiagnosed%3A%20Of%20the,million%20Americans%20are%20diagnosed%20with%20diabetes%20every%20year
  4. Kühl, C. (1998). Etiology and pathogenesis of gestational diabetes. Diabetes care, 21 Suppl 2, B19-26. https://pubmed.ncbi.nlm.nih.gov/9704223/
  5. Wexler, DJ. (2020). Initial management of hyperglycemia in adults with type 2 diabetes mellitus. UpToDate. Retrieved April 16. 2021, from https://www.uptodate.com/contents/initial-management-of-hyperglycemia-in-adults-with-type-2-diabetes-mellitus
  6. Carlsson, S. (2019). Etiology and pathogenesis of latent autoimmune diabetes in adults (LADA) compared to type 2 diabetes. Frontiers in Physiology 10:320. Retrieved April 16, 2021, from https://pubmed.ncbi.nlm.nih.gov/30971952/
  7. Bell RA, et al. (2009). Diabetes in non-Hispanic white youth: prevalence, incidence, and clinical characteristics: the SEARCH for Diabetes in Youth Study. Diabetes Care 32 Suppl 2(Suppl 2):S102–S111. https://pubmed.ncbi.nlm.nih.gov/19246575/ 
  8. Mayer-Davis EJ, et al. (2018). ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 19 Suppl 27(Suppl 27):7–19. https://pubmed.ncbi.nlm.nih.gov/30226024/

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