Beta cell (dys)function in non-diabetic offspring of diabetic patients

Abstract

Aims/hypothesis The first-degree offspring of patients with type 2 diabetes are prone to develop type 2 diabetes, and have both insulin resistance and beta cell impairment. However, it is still unclear whether both pathophysiological features are inseparably combined and which is the outstanding determinant in the offspring. Methods Glucose metabolism, insulin sensitivity (calculated as M value divided by insulin [M/I]) and beta cell function were studied in the offspring of individuals with type 2 diabetes (n=187; 57% females; age 43.8±8.1 years; BMI 26.8±4.5 kg/m 2 ) and in individuals without a family history of type 2 diabetes (controls, n=519, 55% females; age 43.4± 8.2 years; BMI 26.4± 3.7 kg/m 2 , no significant differences between the groups for any characteristic) by performance of 75 g OGTT and 2 h hyperinsulinaemic (40 mU min −1 m −2 )-isoglycaemic clamp tests. Beta cell function was evaluated by calculating insulinogenic index (IGI) from C-peptide AUC:glucose AUC ratios from the first hour of OGTT (IGI[60 min]) and from the total OGTT (IGI[120 min]). Results During the OGTT, the offspring of individuals with type 2 diabetes showed 4-14% higher plasma glucose from 30 to 120 min (p<0.05) and 20-29% higher serum insulin from 90 to 120 min, but decreased IGI(60 min) and IGI (120 min) (p<0.05). M/I was 11% lower in the offspring of affected individuals than in controls (p<0.01). To study the offspring of patients with type 2 diabetes with insulin sensitivity similar to that of the control group, the offspring of affected patients were divided into M/I quartiles. Those in the third M/I quartile showed M/I values and major anthropometric characteristics similar to those of the controls, but insulin AUC and C-peptide AUC values were lower in the first hour and the total OGTT (p<0.05). The third M/I quartile had lower IGI values at 60 min and 120 min: 11% and 14% lower, respectively (p<0.02). Conclusions/interpretation The first-degree offspring of type 2 diabetic patients show insulin resistance and beta cell dysfunction in response to oral glucose challenge. Beta cell impairment exists in insulin-sensitive offspring of patients with type 2 diabetes, suggesting beta cell dysfunction to be a major defect determining diabetes development in diabetic offspring.

Serum visfatin and vaspin levels in normoglycemic first-degree relatives of Iranian patients with type 2 diabetes mellitus

“…They also have defects in beta cell function at a time when they are not hyperglycemic, and this reduction affects insulin and amylin responses to glucose stimulation [20]. Since both insulin sensitivity and beta cell dysfunction predict conversion to diabetes [32,33], FDRs are at increased risk of type 2 diabetes [21]. A recent large population study [33] showed that beta cell impairment exists in the offspring of type 2 diabetes patients, even in the absence of insulin resistance, suggesting that beta cell dysfunction is the outstanding determinant for the development of diabetes mellitus in this group.…”

The normoglycemic first-degree relatives of patients with type 2 diabetes mellitus have low circulating omentin-1 and adiponectin levels

“…They also have defects in b cell function when they are not hyperglycemic, and this reduction affects insulin and amylin responses to glucose stimulation [21]. Since both insulin sensitivity and b cell dysfunction predict conversion to diabetes [14,22], FDRs are at increased risk of type 2 diabetes [15]. Therefore, they are very good available models to study the early development of insulin resistance in a pre-diabetes state.…”

“…The results of a large population study [14] showed that b cell impairment exists in the offspring of type 2 diabetes patients, even in the absence of insulin resistance. Thus, b cell dysfunction is the outstanding determinant for the development of diabetes mellitus in this group.…”

Effects of smoking cessation on β-cell function, insulin sensitivity, body weight, and appetite

“…b-cell secretion and insulin sensitivity " b-cell secretion was evaluated as the C-peptide response to the glycemic stimulus using the insulinogenic index (IGI), an OGTTbased measure which has been widely used (23). The IGI40 is calculated as the ratio between C-peptide area under the curve (AUC) and glucose AUC in the time interval from 0 to 40 min of the OGTT (23).…”

“…The IGI40 is calculated as the ratio between C-peptide area under the curve (AUC) and glucose AUC in the time interval from 0 to 40 min of the OGTT (23). The choice of 40 min derives from the fact that at 40 min the C-peptide concentration reached its peak value (23).…”