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The endocrine pancreas consists of the islets of Langerhans, which contain four major cell types-F, ct,5, and PP (pancreatic polypeptide) cells.
Cell Hormone secreted
Cell Insulin
Cell Glucagon
Cells Somatostatin
Cells Pancreatic polypeptide (vasoactive intestinal peptide, VIP)
Diabetes Mellitus
Diabetes mellitus is a group of metabolic disorders having the feature of hyperglycemia which results From either defect in insulin secretion, insulin action, or both. The diagnosis of diabetes is established by elevation of plasma glucose by any one of three criteria:
  • A random plasma glucose concentration of 200 mg/dL or higher, with classical signs and symptoms
  • A fasting glucose concentration of 126 mg/dL or higher on more than one occasion, or
  • An abnormal oral glucose tolerance test (OGTT), in which the glucose concentration is 200 mg/dl or higher 2 hours after a standard carbohydrate load (75 gm of glucose).
  • A level of glycated hemoglobin (HbA1c) > 6.5 g/dL (accepted as an additional criteria for the diagnosis of DM by American Diabetic Association.
Apart from over diabetics, the following types of individuals are there:
  • Euglycemic individuals: serum fasting glucose values less than 110 mg/dl, or less than 140 mg/dL following an OGTT
  • lmpaired glucose tolerance: serum fasting glucose greater than 110 but less than 125 mg/dL, or OCTT values of greater than 140 but less than 200 mg/dL. It is associated with increased risk of progressing to diabetes.
The insulin gene is expressed in the B cells of the pancreatic islets. Preproinsulin synthesized in the rough endoplasmic reticulum is delivered to the Golgi apparatus where it is converted to insulin and a cleavage peptide, C-peptide.
The vast majority of cases of diabetes fall into one of two broad classes:
  • Type 1 diabetes: it is characterized by an absolute deficiency of insulin secretion caused by pancreatic -cell destruction, usually resulting from an autoimmune attack.
  • Type 2 diabetes; it is caused by a "relative insulin deficiency'' due to combination of peripheral resistance to insulin action and an inadequate compensatory response of insulin secretion by the pancreatic cells.

Pathogenesis Of Type 1 Diabetes Mellitus
The following are the risk factors for the development of type 1 DM:
  1. Genetic factors: these could affect
    HLA genes (commonest locus being affected is on chromosome 6p21 (HLA D) like
    HLA DR3/DR4 with DQ8 haplotype
    The non HLA genes like that for insulin or polymorphism in CD25 (normally regulated the function of T cells)
  2. Environmental factors: viral infections like coxsackie B, mumps, rubella or cytomegalovirus.
    The failure of self tolerance in T cells is the main defect in type 1 DM. The autoreactive Tcells (TH1 cells and CD8+ cytotoxic T cells) get activated and cause p cell injury resulting in the reduction of p cell mass. Autoantibodies against a variety of B-cell antigens, including insulin, islet cell autoantigen 512 and glutamic acid decarboxylase are also found in the patients.
Pathogenesis Of Type 2 Diabetes Mellitus
The disease is characterized by the following metabolic defects:
  • Insulin resistance: it is defined as resistance to the effects of insulin on glucose uptake, metabolism, or storage. It is a characteristic feature of most individuals with type 2 diabetes.
  • B-cell dysfunction: inadequate insulin secretion in the presence of insulin resistance and hyperglycemia
There is no autoimmune basis of type 2 DM. The insulin resistance is being contributed maximally by the loss of sensitivity in the hepatocytes.

An increase in the number of and size of islets is characteristic of non diabetic infants of mothers.

Monogenic Forms Of Diabetes
The monogenic forms of diabetes can be due to the following causes:
Primary defect in-cell function Defect in insulin-insulin receptor signaling
Autosomal-dominant inheritance with high penetrance
Early onset (usally before age 25)
Absence of obesity
Lack of islet cell autoantibodies
Type A insulin resistance (severe insulin resistance+hyperinsulinemia+DM)
Lipoatrophic diabetes (insulin resistance + hypertriglyceridemia + DM + acanthosis nigricans + hepatic steatosis)

Clinical Features Of DM

Clinical Features Of DM

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