National University of Rwanda Family and Community Medicine

Diabetes Mellitus Type I

KABERA Ren, MD PGY IV Resident Family and Community Medicine National University of Rwanda

Plan
Definition Diagnosis criteria Epidemiology Pathophysiology Prevention and treatment

Definition
Diabetes mellitus encompasses a heterogeneous group of disorders defined by a derangement in carbohydrate metabolism caused by a defect in either insulin secretion or insulin action

Diagnosis criteria
Randomly measured plasma concentration of glucose of 200 mg/dL or greater with classic signs and symptoms of diabetes (polyuria, polydipsia, weight loss, fatigue) or Fasting plasma concentration of glucose 126 mg/dL or greater with no caloric intake for at least 8 hours previously or Abnormal result of an oral glucose tolerance test (OGTT)[1.75 g/kg by mouth of anhydrous glucose dissolved in water (to a maximum of 75 g)] and plasma concentration of glucose after glucose load of 200 mg/dL or Greater Any one of these criteria must be repeated on a subsequent day to confirm the diagnosis, unless there is unequivocal hyperglycemia with acute metabolic decompensation (diabetic ketoacidosis).

Epidemiology
The worldwide prevalence of DM has risen dramatically over the past two decades, From an estimated 30 million cases in 1985 to 177 million in 2000 Based on current trends, >360 million individuals will have diabetes by the year 2030 The prevalence of type 2 DM is rising much more rapidly Increasing obesity and reduced activity levels as countries become more industrialized.

DM I
The result of interactions of genetic, environmental, and immunologic factors that ultimately lead to the destruction of the pancreatic beta cells and insulin deficiency. Autoimmune process with linkage to particular HLA types. Presence of autoantibodies directed against b cells Insulin deficient autoantibody-positive insulin level and C-peptide decreased Ketosis prone Frequently younger than 18 yrs

Pathophysiology
Other islet cell types [alpha cells (glucagon-producing), delta cells (somatostatin-producing), or PP cells (pancreatic polypeptide-producing)] Functionally and embryologically similar to beta cells and express most of the same proteins as beta cells, Spared from the autoimmune process. Pathologically, the pancreatic islets are infiltrated with lymphocytes (in a process termed insulitis). After all beta cells are destroyed, the inflammatory process abates, the islets become atrophic, and most immunologic markers disappear

Pathophysiology
Abnormalities in the humoral and cellular arms of the immune system: Islet cell autoantibodies; Activated lymphocytes in the islets, peripancreatic lymph nodes, and systemic circulation; T lymphocytes that proliferate when stimulated with islet proteins; and Release of cytokines within the insulitis. Beta cells seem to be particularly susceptible to the toxic effect of some cytokines [tumor necrosis factor (TNF-), interferon , and interleukin 1 (IL-1)]. The islet destruction is mediated by T lymphocytes rather than islet autoantibodies, as these antibodies do not generally react with the cell surface of islet cells

Pancreatic Hormones and Insulin Receptor Agonists

The bulk of the pancreas is an exocrine gland secreting pancreatic fluid into the duodenum after a meal. Inside the pancreas are millions of clusters of cells called islets of Langerhans. The islets are endocrine tissue containing four types of cells. In order of abundance, they are: beta cells, which secrete insulin and amylin; alpha cells, which secrete glucagon; delta cells, which secrete somatostatin gamma cells, which secrete a polypeptide

Pancreatic Hormones and Insulin Receptor Agonists

Pancreatic Hormones Insulin : Regular insulin ,Insulin analogs, Pre-mixed insulin Amylin Glucagon Somatostatin Pancreatic Polypeptide

Insulin
Insulin is an anabolic hormone. Secretion of insulin in response to feeding governs use of glucose in peripheral tissues, such as muscle, through enhanced glucose uptake and glycolysis. Insulin facilitates energy storage in the forms of glycogen, fat, and protein. Adipogenesis is approximately 10 times more sensitive to the effects of insulin than are the carbohydrate effects. The effects on carbohydrate metabolism are the first manifestation of relative insulin deficiency Hyperglycemia is caused by limited glucose uptake into cells and by diminished insulin effects on the liver with increased hepatic glucose production from both breakdown of glycogen stores and increased gluconeogenesis.

Insulin

Insulin

Clinical presentation
As serum level of glucose exceeds the renal threshold for glucose reabsorption at approximately 180 mg/dL, Osmotic diuresis occurs, and the classic symptoms of polyuria and compensatory polydipsia ensue. The urinary symptoms may prompt evaluation for secondary enuresis or for associated candidal diaper dermatitis or vaginitis.

Clinical presentation
Fatigue and weakness are common from nocturia, disturbed sleep, and breakdown of protein from muscle to provide amino acids as substrate for gluconeogenesis. Polyphagia and weight loss also are common. Visual disturbance can be caused by diffusion of glucose into the lens and subsequent swelling. Further elevation in serum level of glucose, and hence osmolality, can cause lethargy

Clinical presentation

Management of KDA
Confirm diagnosis (plasma glucose, positive serum ketones, metabolic acidosis). Admit to hospital; intensive-care setting may be necessary for frequent monitoring or if pH < 7.00 or unconscious. Assess: Serum electrolytes (K+, Na+, Mg2+, Cl-, bicarbonate, phosphate) Acid-base statuspH, HCO3-, PCO2, b-hydroxybutyrate Renal function (creatinine, urine output) Replace fluids: 23 L of 0.9% saline over first 13 h (1015 mL/kg per hour); subsequently, 0.45% saline at 150300 mL/h; change to 5% glucose and 0.45% saline at 100200 mL/h when plasma glucose reaches 250 mg/dL (14 mmol/L).

Management DKA
Administer short-acting insulin: IV (0.1 units/kg) or IM (0.3 units/kg), then 0.1 units/kg per hour by continuous IV infusion; increase 2- to 3-fold if no response by 24 h. If initial serum potassium is < 3.3 mmol/L (3.3 meq/L), do not administer insulin until the potassium is corrected to > 3.3 mmol/L Assess patient: What precipitated the episode (noncompliance, infection, trauma, infarction, cocaine)? Initiate appropriate workup for precipitating event (cultures, CXR, ECG). Measure capillary glucose every 12 h; measure electrolytes (especially K+, bicarbonate, phosphate) and anion gap every 4 h for first 24 h. Monitor blood pressure, pulse, respirations, mental status, fluid intake and output every 14 h.

Management of KDA
Replace K+: 10 meq/h when plasma K+ < 5.5 meq/L, ECG normal, urine flow and normal creatinine documented; administer 4080 meq/h when plasma K+ < 3.5 meq/L or if bicarbonate is given. Continue above until patient is stable, glucose goal is 150 250 mg/dL, and acidosis is resolved. Insulin infusion may be decreased to 0.050.1 units/kg per hour. Administer intermediate or long-acting insulin as soon as patient is eating. Allow for overlap in insulin infusion and subcutaneous insulin injection

Prevention and Treatment

Prevention of Type 1 DM A number of interventions have successfully delayed or prevented diabetes in animal models. Though results in animal models are promising, these interventions have not been successful in preventing type 1 DM in humans. The Diabetes Prevention Trialtype 1 concluded that administering insulin (IV or PO) to individuals at high risk for developing type 1 DM did not prevent type 1 DM. In patients with new-onset type 1 diabetes, treatment with anti-CD3 monoclonal antibodies has recently been shown to slow the decline in Cpeptide levels

Management DM I
Insulatard 2x/d: This is the simplest of the insulin regimens. While it may help with the control of basal glycemia, it does not cover the meal time rise in glucose. For many patients with diabetes type 2, this will be enough to achieve glycemic control. A good starting dose is 0.8 1.0 units/kg/day (type 1) or 0.3 0.6 units/kg/day (type 2), Divided between a morning (60%) and evening dose (40%). Injections should be given around 7 am and 7 pm.

Management DM I
Mixte 2x/d: Another regimen that requires only 2 injections per day. In some cases, it better controls meal time hyperglycemia, particularly in Rwandans, since the diet is high in carbohydrates. However, lunch is still not covered. Also, for some patients, the fixed ratio of 70/30 will not have enough regular insulin (patients may require a ratio closer to 50/50). Starting at a dose of 0.3 0.6 units/kg/day, divided between a morning and evening dose, is reasonable. Injection should be given 20 30 minutes before breakfast and 20 30 minutes before dinner.

Management DM I
Insulin Lente/Rapide 2x/day: For patients who need to have the individual doses of lente and rapide adjusted (instead of the fixed ratio of insulin mixte 70/30), this regimen may work better. The patient must mix insulin from two vials (lente and rapide) and give the injection 2x/day (at 7 am and 7 pm). The morning or evening doses of lente or rapide can be individually adjusted. Mid-day hyperglycemia can be controlled with the morning dose of lente.

Chronic Complications of Diabetes Mellitus

Microvascular Eye disease Retinopathy (nonproliferative/proliferative) Macular edema Neuropathy Sensory and motor (mono- and polyneuropathy) Autonomic Nephropathy

Chronic complications
Macrovascular Coronary artery disease Peripheral arterial disease Cerebrovascular disease

Chronic complications
Other Gastrointestinal (gastroparesis, diarrhea) Genitourinary (uropathy/sexual dysfunction) Dermatologic Infectious Cataracts Glaucoma Periodontal disease

References
Harrison's Principles of Internal Medicine Chronic Care Integration for Endemic Non-Communicable Diseases ,Rwanda edition: cardiac, renal, diabetes, pulmonary, and palliative care(paterner in ealt Rudolph's Pediatrics

End

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