Compare/contrast Diabetes Mellitus Type I to Diabetes Mellitus Type II at the cellular and chemical levels. Can you see any reason/explanation why members of the same family might be more prone to developing this disease, even if it is not hereditary? Please include references

 

CELLULAR Type I diabetes is an autoimmune disease in which islet β cells are destroyed primarily by T lymphocytes reacting against as yet β-cell antigens. Therefore, in Type I Diabetes Mellitus there is insulitis, marked atrophy and depletion of β cells. On the other hand, Type II diabetes is characterized by Focal atrophy and amyloid deposition, absence of insulitis and mild β cells depletion.

Type I diabetes mellitus, T lymphocytes react against β-cell antigens and cause cell damage. These T cells include CD4+ T cells of the T_H1 subset, which cause tissue injury by activating macrophages, and CD8+ cytotoxic T lymphocytes, which directly kill β cells and also secrete cytokines that activate macrophages. while in Type II diabetes mellitus there are increased Intracellular triglycerides and products of fatty acid metabolism which are potent inhibitors of insulin signaling and result in an acquired insulin resistance state

CHEMICAL In Type I diabetes the islet β cells are destroyed leading to gradual reduction in Insulin production and eventually to the complete deficiency of insulin and therefore to dependence on exogenous Insulin which gave it the original name Insulin-dependent Diabetes Mellitus. Type II type 2 diabetes on the other hand is characterized by a decreased ability of peripheral tissues to respond to insulin, that is, insulin resistance) and β-cell dysfunction that is manifested as inadequate insulin secretion in the face of insulin resistance and hyperglycemia.

Diabetic ketoacidosis (DKA) is a serious complication of type I diabetes but may also occur in type II diabetes, though not as commonly and not to as marked an extent. These patients have marked insulin deficiency, and the release of the catecholamine hormone epinephrine blocks any residual insulin action and stimulates the release of glucagon. The insulin deficiency coupled with glucagon excess decreases peripheral utilization of glucose while increasing gluconeogenesis. The hyperglycemia causes an osmotic diuresis and dehydration characteristic of the ketoacidotic state. The second major effect of an alteration in the insulin:glucagon ratio is activation of the ketogenic machinery. Insulin deficiency stimulates lipoprotein lipase, with resultant excessive breakdown of adipose stores, and an increase in levels of free fatty acids. When these free fatty acids reach the liver, they are esterified to fatty acyl CoA. Oxidation of fatty acyl CoA molecules within the hepatic mitochondria produces ketone bodies.

Type I Diabetes Mellitus responds well to Insulin therapy while Type II Diabetes Mellitus responds well to oral drugs that lower the Insulin resistance or increase insulin release from islet cells e.g biguanides (Metformin) or sulfony ureas (chlopropramide)

AGE Type I Diabetes Mellitus is characterized by early onset, mostly before 20 years of age whereas Type II Diabetes Mellitus is characterized by late onset, mostly above 30 years of age.

WEIGHT Type I Diabetes Mellitus is characterized by normal or low weight whereas Type II Diabetes Mellitus patients are almost always obese.

GENETICS In Type I Diabetes Mellitus there is 30-70% concordance in twins with Linkage to MHC Class II HLA genes in Type II Diabetes Mellitus there is 50-90% concordance in twins with no linkage to HLA genes.

Members of the same family can develop Diabetes Mellitus and often do, for the following reasons

1. GENETIC STUDIES. The principal susceptibility locus for type I diabetes resides in the region that encodes the class II molecules of the MHC on chromosome 6p21 (HLA-D). 90% to 95% of Caucasians with type 1 diabetes have HLA-DR3, DR4, or both, in contrast to about 40% of normal subjects; and 40% to 50% of patients are DR3/DR4 heterozygotes, in contrast to 5% of normal subjects. This coupled with the other environmental factors such as viral infections that are likely to effect members of the same family mean that members of a family will be susceptible to the autoimmune process that precedes Diabetes Mellitus Type I whereas Type II Diabetes Mellitus is associated with polymorphisms as opposed to single gene mutations but also has other environmental factors that are likely to be shared amongst members of a family, e.g obesity and sedentary lifestyles.
2. EPIDEMIOLOGICAL STUDIES. In Type I Diabetes Mellitus there is 30-70% concordance in twins whereas in Type II Diabetes Mellitus the concordance rate in twins is 50% to 90%, while among first-degree relatives with type 2 diabetes (and in fraternal twins), the risk of developing the disease is 20% to 40%, compared to 5% to 7% in the population at large

Source: Robbins and Cotran Pathologic Basis of Disease, 7th edition.