Progressive β Cell Failure in Type 2 Diabetes Mellitus: Microvascular Pancreatic Isletopathy?

Background: UKPDS suggested relentless deterioration of β cell function as a part of natural course of type 2 diabetes mellitus. However, the course was apparently not universal since many patients maintained glycemic goal (HbA1c < 7.0%) at 9 years while receiving conventional life style programs consisting of diet and exercise or/and oral agents. Moreover, β cell failure occurred around the same time as the time of onset of microvascular complications. Finally, the exact mechanism of progressive β cell failure remains to be defined. It is plausible that β cell failure may be due to fibrosis of pancreatic islets secondary to microangiopathy since no organ or tissue is exempt from this complication. Objective: To assess epidemiologic correlation between presence of b cell failure and microvascular complications by determining the prevalence of β cell failure in subjects with type 2 diabetes with increasing number of known microvascular complications. Methods: 650 Subjects with ages 40-75 years and duration of DM 4-23 years were divided into 4 groups according to number of microvascular complications, e.g. retinopathy, nephropathy, and neuropathy. β cell failure (β - ve ) is defined as HbA1c > 7.0% with any therapy or HbA1c < 7.0% with insulin, either monotherapy or in combination with oral agents. β cell function is deemed “preserved” (β + ve) with HbA1c < 7.0% with treatment consisting of life style program or/and oral drugs. Results: Prevalence of b cell failure progressively rose with increasing number of microvascular complications from 0 to 2 with no further significant rise with 3 complications whereas subjects with preserved β cell function declined with increasing number of microvascular complications (p < 0.01 for both groups). Significant relationships were also noted between the age and the duration of diabetes and prevalence of β cell failure (p < 0.01). The relative risks rose progressively for β cell failure/β cell preserved with increasing number of microvascular complications as well as the greater duration of Diabetes. However, a significantly (p < 0.01) higher relative risk for β cell failure persisted for rising number of microvascular complications even after eliminating the influence of age and duration of diabetes. Conclusion: β cell failure may be a manifestation of microvascular pancreatic isletopathy similar to other microvascular complications.