Diabetes Mellitus Diagnosis & Clinical Assessment PDF

Diabetes Mellitus Diagnosis & Clinical Assessment ILOs At the end of this session, the student will be able to: ▪ Define hyperglycemia from a clinical point of view. ▪ Identify the diagnostic criteria of diabetes mellitus. ▪ Classify diabetes and identify its types; ty...

Diabetes Mellitus Diagnosis & Clinical Assessment ILOs At the end of this session, the student will be able to: ▪ Define hyperglycemia from a clinical point of view. ▪ Identify the diagnostic criteria of diabetes mellitus. ▪ Classify diabetes and identify its types; type 1 diabetes, type 2 diabetes, and secondary diabetes. ▪ Differentiate between type 1 diabetes and type 2 diabetes. ▪ Understand the pathogenesis of different types of diabetes mellitus. Classification & Pathogenesis Type 1 Diabetes Mellitus Autoimmune destruction of pancreatic islet B cell. Occurs at any age but most commonly arises in children and young adults with a peak incidence at age 10-14 years. Usually associated with ketosis in its untreated state. Exogenous insulin is therefore required to reverse the catabolic state and prevent ketosis. Genetic factors: Family members are at increased lifetime risk. Environmental factors: may play a role; Type 1 diabetes is more common in Scandinavian countries and becomes progressively less frequent nearer to the equator. Breastfeeding in the first 6 months of life: protective. The onset of diabetes is usually rapid. Patients frequently have diabetic ketoacidosis at presentation. Positive autoantibodies against islet antigens. Approximately 5% of subjects have no evidence of pancreatic B cell autoimmunity. This subgroup has been classified as "idiopathic type 1 diabetes “or "type 1B." 1 Type 2 Diabetes Mellitus Non-immune causes of pancreatic B cell loss with variable degree of tissue insensitivity to insulin; “insulin resistance”. The residual beta cell function is sufficient to prevent ketoacidosis but is inadequate to prevent hyperglycemia. Used to occur predominantly in adults, but it is now frequently encountered in children and adolescents. Genetic and environmental factors combine to cause both beta cell loss and insulin resistance. Strong genetic influences: 70% in monozygotic twins whenever type 2 diabetes develops in one twin. Genome-wide association studies have identified 143 risk variants and putative regulator mechanisms for type 2 diabetes. Obesity is the most important environmental factor causing insulin resistance. Visceral obesity (accumulation of fat in the omental and mesenteric regions) correlates with insulin resistance. Subcutaneous abdominal fat seems to have less of an association with insulin insensitivity. Exercise may affect the deposition of visceral fat. Other Specific Types of Diabetes: Maturity-onset diabetes of the young (MODY) Monogenic disorders, characterized by non-insulin requiring diabetes, with autosomal dominant inheritance and an age at onset of 25 years or younger. Patients are non-obese, and their hyperglycemia is due to impaired secretion of insulin. Six types of MODY have been described. Patients younger than 30 years with negative autoantibodies are candidates for genetic screening for MODY. MODY 3 (due to mutations in hepatic nuclear factor 1 alpha) is the most common form, accounting for two-thirds of all MODY cases. Initially, patients with MODY 3 are responsive to SU, but later, progressive beta cell failure will end up with insulin requirement. 2 Secondary Diabetes Endocrine tumours secreting growth hormone, glucocorticoids, catecholamines, glucagon, or somatostatin can cause glucose intolerance. Peripheral responsiveness to insulin is impaired. With excess of glucocorticoids, catecholamines, or glucagon, increased hepatic output of glucose is a contributory factor. In the case of catecholamines, decreased insulin release is an additional factors in producing carbohydrate intolerance. Hyperglycemia typically resolves when the hormone excess is resolved. Many drugs are associated with carbohydrate intolerance or frank diabetes. The drugs act by decreasing insulin secretion or by increasing insulin resistance or both. Cyclosporine and tacrolimus impair insulin secretion; sirolimus principally increases insulin resistance. These agents contribute to the development of new-onset diabetes after transplantation. Corticosteroids increase insulin resistance but may also have an effect on beta cell function. 3  Thiazide diuretics and beta-blockers modestly increase the risk for diabetes. Atypical antipsychotics, particularly olanzapine and clozapine, are associated with an increased risk of glucose intolerance. These drugs cause weight gain and insulin resistance but may also impair beta cell function. Chronic pancreatitis or subtotal pancreatectomy reduces the number of functioning B cells and can result in a metabolic derangement very similar to that of type 1 diabetes. However, the concomitant reduction in pancreatic A cells may reduce glucagon secretion so that relatively lower doses of insulin replacement are needed. Clinical Findings of Diabetes: Symptoms & Signs: Type 1 Diabetes As absolute insulin deficiency is of acute onset, there is an abrupt increase in urination, thirst, blurred vision, weight loss, paresthesias, and altered level of consciousness. Ketoacidosis exacerbates dehydration and hyperosmolality by producing anorexia, nausea, and vomiting, interfering with oral fluid replacement. A. Increased urination and thirst: Consequences of osmotic diuresis secondary to sustained hyperglycemia. The diuresis results in a loss of glucose as well as free water and electrolytes in the urine. 4 B. Blurred vision: As the eye lens is exposed to hyperosmolar fluids, blurred vision often develops. C. Weight Loss: Despite normal or increased appetite, weight loss is a common feature of type 1. The weight loss is initially due to depletion of water, glycogen, and triglycerides; Thereafter, reduced muscle mass occurs as amino acids are diverted to form glucose and ketone bodies. Lowered plasma volume produces symptoms of postural hypotension, which is a serious prognostic sign. Total body potassium loss and the general catabolism of muscle protein contribute to the weakness. D. Paresthesias: Paresthesias may be present at the time of diagnosis. They reflect a temporary dysfunction of peripheral sensory nerves “neurotoxicity” due to hyperglycemia. Clears as insulin replacement restores glycemic levels closer to normal. E. The level of consciousness: Can vary depending on the degree of hyperosmolality. Sufficient water intake is maintained, and patients remain relatively alert. When vomiting occurs, due to ketoacidosis, dehydration progresses and compensatory mechanisms become inadequate to keep normal serum osmolality. Under these circumstances, stupor or even coma may occur. The fruity breath odour of acetone further suggests the diagnosis of DKA. Increased urination and thirst may be presenting symptoms in some patients with type 2 diabetes. Many other patients have an insidious onset hyperglycemia and are asymptomatic initially. Type 2 diabetes may be detected only during routine laboratory studies. Occasionally, when the disease has been undiagnosed for some time, patients may present with neuropathic or cardiovascular complications. Hyperglycemic hyperosmolar state can also be present when the serum osmolality exceeds 320-330 mOsm/L. In these cases, patients are profoundly dehydrated, hypotensive, lethargic, or comatosed but without acidotic breathing. 5 Symptoms & Signs: Type 2 Diabetes: A. Skin manifestations: Skin infections: are common. Generalized pruritus and symptoms of vaginitis are frequently the initial complaints of women. Diabetes should be suspected in women with chronic candidal vulvovaginitis. Acanthosis nigricans: associated with significant insulin resistance. The skin in the axilla, groin, and back of the neck is hyperpigmented and hyperkeratotic. Eruptive xanthomas: on the flexor surface of the limbs and on the buttocks and lipemia retinalis due to diabetic dyslipidemia can occur, especially with hypertriglyceridemia. B. Body built: Overweight or obese patients frequently have type 2 diabetes. Even those who are not significantly obese often have characteristic localization of fat deposits on the upper segment of the body (particularly the abdomen) and relatively less fat on the limbs. This centripetal fat distribution is characterized by a high waist circumference. A waist circumference larger than 102 cm in men and 88 cm in women is associated with an increased risk of type 2 diabetes. C. Obstetrical complications: Type 2 diabetes should be considered in women who have delivered babies larger than 4 kg or have had polyhydramnios, preeclampsia, or unexplained fetal loss. Laboratory Findings of Diabetes: 1. Urine Glucose: Can be detected by the use of a paper strip impregnated with a glucose oxidase system, which is sensitive to as little as 100 mg/dL glucose in urine. Non-diabetic glycosuria (renal glycosuria) is a benign asymptomatic condition where glucose appears in the urine despite a normal amount of glucose in the blood. Its cause may vary from mutations in the SGLT2 gene (familial renal glycosuria) to dysfunction of the proximal renal tubule (Fanconi syndrome, chronic kidney disease). 6  It may occur also during pregnancy, a consequence of the increased load of glucose presented to the tubules by the elevated GFR during pregnancy. As many as 50% of pregnant women normally have demonstrable sugar in the urine, especially during the third and fourth months. 2. Urine and blood ketones: Qualitative detection of ketone bodies can be accomplished by nitroprusside tests. This test does not detect beta-hydroxybutyric acid, the earliest ketone body to appear. However, this test is usually adequate for clinical purposes. Many laboratories measure beta-hydroxybutyric acid, and there are meters available for patient use that measures beta-hydroxybutyric acid levels in capillary glucose samples. 3.Fasting Plasma glucose: Glucose is 10-15% higher in plasma than in whole blood because structural components of blood cells are absent. A plasma glucose level of 126 mg/dL or higher on more than one occasion after at least 8 hours of fasting is diagnostic of diabetes. Fasting plasma glucose levels of 100-125 mg/dL are associated with increased risk of diabetes (impaired fasting glucose tolerance). 7 4.Oral glucose tolerance test (OGTT): If the fasting plasma glucose level is less than 126 mg/dL when diabetes is suspected, then a standardized oral glucose tolerance test may be done. In order to optimize insulin secretion and effectiveness, a minimum of 150-200 g of carbohydrate per day should be included in the diet for 3 days preceding the test. The patient should eat nothing after midnight prior to the test day. On the morning of the test, patients are then given 75 g of glucose in 300 ml of water. The glucose load is consumed within 5 minutes. Blood samples for plasma glucose are obtained at 0 and 120 minutes after ingestion of glucose. An oral glucose tolerance test is normal if the fasting plasma glucose value is less than 100 mg/dL and the 2-hour value falls below 140 mg/dL. A fasting value of 126 mg/dl or higher or a 2-hour value of greater than 200 mg/dL is diagnostic of diabetes. Patients with a 2-hour value of 140-199 mg/dL have impaired glucose tolerance (IGT). 8 5.Glycated hemoglobin (hemoglobin A1c): Measures the amount of Hb that becomes glycated. Normally, HbA1c comprises 4-6% of total hemoglobin A. Since HbA1c circulates within red blood cells whose life span lasts up to 120 days, it generally reflects the state of glycemia over the preceding 8-12 weeks. Measurements should be made in patients with diabetes at 3-month intervals, to assess their glycemic control. A cut-off value of 6.5% is diagnostic for diabetes. The advantages of using the HbA1c to diagnose diabetes is that there is no need to fast; it has lower intra-individual variability than the fasting glucose. People with HbA1c levels of 5.7-6.4% should be considered at high risk for developing diabetes (prediabetes). 6. Serum fructosamine: Serum fructosamine is formed by nonenzymatic glycosylation of serum proteins (pre-dominantly albumin). Since serum albumin has a much shorter half-life than hemoglobin, serum fructosamine generally reflects the state of glycemic control for only the preceding 1-2 weeks. Reductions in serum albumin (e.g. nephrotic state, protein-losing enteropathy, or hepatic diease) will falsely lower the serum fructosamine value. When abnormal hemoglobins or hemolytic states affect the interpretation of HbA1c or when a narrower time frame is required, such as during pregnancy, serum fructosamine assays offer some advantage. 7.Self monitoring of blood glucose (SMBG): Capillary blood glucose measurements performed by patients themselves, as outpatients, are extremely useful. A large number of blood glucose meters are available. All are accurate, but they vary with regard to speed, convenience, size of blood samples required, reporting capability, and cost. The accuracy of data obtained by home glucose monitoring does require education of the patient in sampling and measuring procedures. Generally speaking, accuracy here is less than lab measurement of plasma glucose. Impaired circulation to the fingers (for example, in patients with Raynaud disease) will artificially lower fingerstick glucose measurements (pseudo- hypoglycemia). 9 8.Continous glucose monitoring (CGM) systems: A glucose oxidase-based system to measure glucose concentrations in the interstitial fluid. These systems involve inserting a subcutaneous sensor that measures glucose concentrations continuously in the interstitial fluid for 7-14 days. Glucose data are transmitted wirelessly to smartphones or to the screens of insulin pumps. Directional arrows indicate rate and direction of change of glucose levels, and alerts can be set for dangerously low or high glucose values. The percentage of “time in range" (TIR) (glucose levels 70 - 180 mg/day). Time in range (TIR) of 70% or more, corresponds to HbA1c of less than 7%. 9.Lipid profile in diabetes: Circulating lipoproteins are just as dependent on insulin as is the plasma glucose. In type 1 diabetes, uncontrolled hyperglycemia is associated with only a slight elevation of LDL cholesterol and serum triglycerides and little if any change in HDL cholesterol. However, in patients with type 2 diabetes, a distinct "diabetic dyslipidemia" is characteristic of the insulin resistance syndrome. Its features are a high serum triglyceride level (300-400 mg/dL, a low HDL cholesterol (less than 30 mg/dl), and small dense LDL particles. These smaller dense LDL particles are more susceptible to oxidation, which renders them more atherogenic. 10