Asian Indian Prediabetes Study
Condition: Pre Diabetes
MeSH terms: Prediabetic State
Study type: Interventional

Summary: 
      Compared to other races, Indians have higher insulin resistance, poorer pancreatic function
      and a greater risk of developing diabetes, highlighting the importance of early strategies
      for improving insulin sensitivity and improving pancreatic function in Indians to prevent
      diabetes and lower the risk of heart disease.

      A low carbohydrate diet can deplete fat from undesirable places, such as fat around organs in
      the abdominal cavity. In this study, we will determine if restriction of dietary
      carbohydrates will deplete fat in the pancreas and liver, and improve insulin sensitivity and
      early insulin secretion in Indians. These changes may prevent diabetes from developing.
      Hepatic and pancreatic fat will be measured using magnetic resonance imaging. Insulin
      sensitivity and secretion will be measured during an oral glucose tolerance test. In
      addition, this study will investigate if the higher insulin resistance in Indians is due to
      genes that cause the inability to store fat in the legs.

      The results on the type of diet that is more effective for reducing pancreatic and hepatic
      fat is important for informing dietary guidelines on the use of low carbohydrate diets for
      diabetes prevention, particularly in Indians who have a higher risk of developing diabetes.
    

Detailed description: 
      Compared to other races, Indians have a greater risk of developing type 2 diabetes (T2D),
      increased insulin resistance (IR) and more rapid decline in β-cell function, highlighting the
      urgency and importance of early intervention strategies for improving insulin sensitivity and
      preserving/improving β-cell function to prevent T2D and mitigate against the increased
      vascular disease risk.

      Preliminary findings show a reduction in glycemic load selectively depletes visceral and
      ectopic lipid and improves insulin sensitivity and β-cell function in non-diabetic adults.
      The proposed research will investigate if the phenotypic features increasing T2D risk in
      individuals of Indian ancestry (IR and impaired β-cell function) can be favorably modified by
      a low glycemic (LG) intervention, and if the increased IR is attributable to genetic factors
      regulating adipocyte differentiation and function.

      These research objectives will be achieved through a 24-week randomized controlled trial
      (RCT) comparing isocaloric LG versus control diets in Indians with prediabetes. Compared to
      individuals in the control group, those on the LG diet are expected to have greater ectopic
      (pancreas, liver, visceral and intramyocellular) fat depletion assessed with MRI/MRS, and
      improvements in first phase insulin secretion and insulin sensitivity assessed with the
      C-peptide model and oral minimal model, respectively during an OGTT. Reductions in hepatic
      and pancreatic lipids will be associated with improvements in first-phase β-cell response.
      Individuals with a greater number of risk alleles from a 53-SNP IR genetic risk score will
      have lower insulin sensitivity and leg fat, supporting the notion that impaired adipocyte
      differentiation leading to limited peripheral adipose expansion capacity is an important
      etiological factor underpinning IR cardiometabolic disease in Indians.

      The results will broaden the evidence base for effective prevention strategies in this high
      risk population by investigating the effect of the proposed diet intervention on underlying
      physiological and molecular mechanisms implicated in the pathophysiology of T2D in Indians.
    

Intervention name(s): Lifestyle (Diet and Exercise)
Intervention type(s): Other
Intervention description(s): The LG diet will comprise 20% carbohydrate, 30% protein, and 50% fat (<10% saturated fat). It will have a low glycaemic load; include plant and animal protein; non-starchy vegetables and salad greens; and some low-sugar fruit. Participants will be encouraged to incorporate a variety of foods rich in monounsaturated and polyunsaturated fats in their diet.
The control diet will comprise 50% carbohydrate, 20% protein and 30% total fat (<10% saturated fat). It will reflect the Health Promotion Board's (HPB) recommendations to reduce dietary fat, emphasize wholegrains and include a variety of fruits and vegetables. In contrast to the LG diet, the control diet will have a higher glycaemic load with a greater proportion of energy derived from unrefined carbohydrate foods.
Concurrent to the dietary intervention and consistent with physical activity guidelines, all participants will undertake a 60-min structured exercise program incorporating aerobic/ resistance exercises 3-4 days/week.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 24-week parallel arm, randomized controlled trial (RCT)
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Asian Indians; Prediabetes; Insulin Resistance; Low glycaemic diet; Ectopic Fat