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Relation between residual beta cell function and glycemic variability in (pre)type 1 diabetes.
Type 1 diabetes develops when 60 to 90% of insulin-producing beta cells ahve been destroyed. This cell loss leads to greater variability of blood glucose levels both before and after diagnosis. This variability is predictive of progression to clinical onset of diabetes in risk groups and of frequenc of hypoglycemic events in patients. Novel beta cell therapy trials aim to prevent or cure diabetes by trying to preserve or restore functional beta cell mass. In preparation of future trials the collaborating teams of the present application have validated dynamic tests to measure functional beta cell mass in vivo through prolonged stimulation of beta cells by elevated glucose levels (hyperglycemic clamp tests). The present application proposes to measure glycemic variability by continuous glucose monitoring (CGM) and frequent self-monitoring of blood glucose (SBMG) in 40 recent-onset type 1 diabetic patients and in 40 high-risk relatives (>50% 5-year risk of diabetes) (age 12-39 years) as a funtion of their residual functional beta cell mass as determined by hyperglicemic clamp. The participant will undergo 5 clamp tests and 5 periods of glycemic monitoring during a 2-year follow-up. Various parameters of glycemic variability will be derived from CGM and SMBG measurements and correlated with corresponding values of residual beta cell function (anticipated to vary between 10 and 100% of healthy controls in the proposed study groups) and parameters of metabolic control. This should allow to identify treatment goals for functional beta cell mass to be reached in therapy trials in order to avoid frequent hypoglycemia in patients and dysglycemia in risk groups.
Date:1 Jan 2011 → 31 Dec 2016
Keywords:Glycemic variability, Hyperglycemic clamp, Continuous glucose monitoring, High-risk relatives, Type 1 diabetes, Self-minitoring of blood glucose