Assessment of the association between glycemic variability and diabetes-related complications in type 1 and type 2 diabetes.

Chronic hyperglycemia is the main risk factor for the development of diabetes-related complications in both type 1 and type 2 diabetes, but it is thought that frequent or large glucose fluctuations may contribute independently to diabetes-related complications. A systematic literature review was performed using the PubMed, EMBASE and Cochrane Library databases with searches limited to studies published from June 2002 to March 2014, in English and including ≥50 patients. Twenty eight articles were included in the final review. Eighteen studies reported the association between glucose variability and diabetes-related complications exclusively in type 2 diabetes. A positive association between increased variability and microvascular complications and coronary artery disease was consistently reported. Associations between glucose variability and other macrovascular complications were inconsistent in type 2 diabetes. Seven studies examined the association between glucose variability and complications exclusively in type 1 diabetes. Increased glucose variability appears to play a minimal role in the development of micro- and macrovascular complications in type 1 diabetes. Consistent findings suggest that in type 2 diabetes glucose variability is associated with development of microvascular complications. The role of increased glucose variability in terms of microvascular and macrovascular complications in type 1 diabetes is less clear; more data in are needed.

Model based study on monitoring ketone bodies to improve safety in intensive insulin therapy.

AIM: The present study explores new signals (capillary 3betahydroxybutyrate - 3betaOHB) for improving the safety of a closed loop insulin infusion system (external wearable artificial pancreas). METHODS: Data collected during a clinical trial on diabetic subjects including a period of insulin deprivation were interpreted through mathematical models to simulate the effect of monitoring ketone bodies (capillary 3betaOHB, KB) compared to blood glucose in subjects on Continuous Subcutaneous Insulin Infusion (CSII) treatment. RESULTS: The estimation of model coefficients satisfactorily fits experimental data. The evaluation of dynamic changes of capillary 3betaOHB levels showed a more rapid response than blood glucose. CONCLUSIONS: The effect of the combination of monitoring of glucose and ketone bodies can consistently improve the safety and efficacy of the use of a closed loop system for glycemic control in dangerous situations like ketoacidosis. If a subcutaneous glucose-ketone bodies sensor were to become available in the near future it would be a key component of an external artificial pancreas.

Early detection of insulin deprivation in continuous subcutaneous insulin infusion-treated patients with type 1 diabetes.

BACKGROUND: This study was performed to define the clinical relevance of early changes of capillary 3beta-hydroxybutyrate (3betaOHB), for detection of metabolic deterioration before occurrence of overt diabetic ketoacidosis following interruption of continuous subcutaneous insulin infusion (CSII). METHODS: An open clinical trial was performed with eight patients with type 1 diabetes on CSII therapy. After an overnight fast, at 8 a.m. (T0) CSII was interrupted for 4 h. At noon (T240) CSII was re-established, and at 4 p.m. (T480) the study was ended. Blood glucose (BG) and capillary and plasma 3betaOHB were measured at 30-min intervals, plasma insulin at 60-min intervals, and urinary ketones at 120-min intervals. RESULTS: After CSII interruption mean BG increased from 149.8+/-54.4 mg/dL at T0 to 224.8+/-56.2 mg/dL at T240 (P<0.05), and mean capillary 3betaOHB increased from 0.1+/-0.1 mmol/L at T0 to 0.9+/-0.6 mmol/L at T240 (P<0.001). The rate of increase of capillary 3betaOHB was faster and significantly more relevant than that of BG (P<0.05). The restoration of CSII produced a significant reduction of mean BG and capillary 3betaOHB (T480, 119.5+/-24 mg/dL and 0.2+/-0.2 mmol/L, respectively; P<0.05 for both vs. T240). The recovery of capillary 3betaOHB was significantly faster than that of BG (P=0.03). CONCLUSIONS: The dynamic evaluation of changes of capillary 3betaOHB levels can represent a useful support to home BG monitoring in the event of CSII interruption, providing faster information on early metabolic deterioration due to insulin deprivation and allowing preventative action for avoiding the evolution towards overt diabetic ketoacidosis. After reintroduction of insulin infusion the monitoring of the faster recovery of 3betaOHB relative to BG can provide useful information for the prevention of late hypoglycemia due to insulin overinfusion.