Cause of Type 2 Diabetes

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Insulin resistance creates a relative insulin deficiency. Insulin resistance can be due to a number of reasons – tends to occur in those that are obese. Thrifty genotype hypothesis may explain reasons. Consensus is that the aetiology is a multifactorial interaction of environmental and genetic factors

Genetic factors:
• genetic predisposition for Type 2 diabetes is stronger than for Type 1
• concordance rates in monozygotic twins is almost 100%
• magnitude of genetic contribution is unknown
• probably involves several genes

Thrifty genotype hypothesis:
A genetic trait that was important to survival (ability to go without food for extended period) is now detrimental due to abundant food supplies and reductions in physical activity. First proposed by Neel in 1962. Certain populations (largely indigenous populations) have developed what is considered a ‘thrifty gene’ that allows them to survive period of famine when food is in short supply – this ‘thrifty gene’ is associated with a metabolic efficiency that allows storage of calories as fat with minimal energy expenditure. However, when food is plentiful, as occurs in many of these cultures today (the ‘westernisation’ of diet), the ‘thrifty gene’ predisposes to obesity (especially central obesity)  increased risk for development of diabetes

Risk Factors:
80% of those with type 2 diabetes are obese (central fat deposition has greater risk than gluteofemoral)
overeating, obesity and inactivity  high risk for type 2
most of type 2 patients are obese, but only a few obese people develop diabetes
in the Nurses Health Study , there was a 38 fold increase in the risk for developing type 2 diabetes if the BMI > 35kg/m2 and 20 fold if the BMI was 30.0-34.9 kg/m2.

Physical Execise:
Low levels of exercise are a risk factor as exercise increases insulin sensitivity (also helps prevent obesity)


Malnutrition in utero
retrospective analysis has shown an inverse relationship between weight at birth and type 2 diabetes in late adulthood
suggested that malnutrition in utero may damage beta cell development

Important risk factor – principally occur in middle age and elderly

Higher incidence in some ethnic groups

During pregnancy, sensitivity to insulin decreases (placental hormones affect glucose tolerance)  beta cells may not be able to meet this increased need for insulin  gestational diabetes. This increases subsequent risk of developing type 2 diabetes or the hyperglycaemia may persist after delivery (80% at 25 years) – could be type 1 or 2. Increased risk for perinatal mortality and neonatal morbidity.

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