Factors Associated with Glycemic Variability in Patients with Type 2 Diabetes: Focus on Oral Hypoglycemic Agents and Cardiovascular Risk Factors

다국어 초록 (Multilingual Abstract)

Background: The role of glycemic variability (GV) in development of cardiovascular diseases remains controversial, and factors that determine glucose fluctuation in patients with diabetes are unknown. We investigated relationships between GV indices, kinds of oral hypoglycemic agents (OHAs), and cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM).
Methods: We analyzed 209 patients with T2DM. The GV index (standard deviation [SD] and mean absolute glucose change [MAG]) were calculated from 7-point self-monitoring of blood glucose profiles. The patients were classified into four groups according to whether they take OHAs known as GV-lowering (A) and GV-increasing (B): 1 (A only), 2 (neither), 3 (both A and B), and 4 (B only). The 10-year risk for atherosclerotic cardiovascular disease (ASCVD) was calculated using the Pooled Cohort Equations.
Results: GV indices were significantly higher in patients taking sulfonylureas (SUs), but lower in those taking dipeptidyl peptidase-4 inhibitors. In hierarchical regression analysis, the use of SUs remained independent correlates of the SD (β=0.209, P=0.009) and MAG (β=0.214, P=0.011). In four OHA groups, GV indices increased progressively from group 1 to group 4. However, these did not differ according to quartiles of 10-year ASCVD risk.
Conclusion: GV indices correlated significantly with the use of OHAs, particularly SU, and differed significantly according to combination of OHAs. However, cardiovascular risk factors and 10-year ASCVD risk were not related to GV indices. These findings suggest that GV is largely determined by properties of OHAs and not to cardiovascular complications in patients with T2DM.

참고문헌 (Reference)

1 Horvath EM, "Rapid ‘glycaemic swings’ induce nitrosative stress, activate poly(ADP-ribose) polymerase and impair endothelial function in a rat model of diabetes mellitus" 52 : 952-961, 2009

2 Ceriello A, "Postprandial hyperglycemia and diabetes complications: is it time to treat?" 54 : 1-7, 2005

3 Rodbard D, "New and improved methods to characterize glycemic variability using continuous glucose monitoring" 11 : 551-565, 2009

4 Greenbaum CJ, "Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes" 31 : 1966-1971, 2008

5 Service FJ, "Mean amplitude of glycemic excursions, a measure of diabetic instability" 19 : 644-655, 1970

6 Quagliaro L, "Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation" 52 : 2795-2804, 2003

7 Ohkubo Y, "Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study" 28 : 103-117, 1995

8 UK Prospective Diabetes Study (UKPDS) Group, "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)" 352 : 837-853, 1998

9 Borg R, "HbA(1)(c) and mean blood glucose show stronger associations with cardiovascular disease risk factors than do postprandial glycaemia or glucose variability in persons with diabetes: the A1C-Derived Average Glucose (ADAG) study" 54 : 69-72, 2011

10 Kohnert KD, "Glycemic variability correlates strongly with postprandial beta-cell dysfunction in a segment of type 2 diabetic patients using oral hypoglycemic agents" 32 : 1058-1062, 2009

11 Hermanides J, "Glucose variability is associated with intensive care unit mortality" 38 : 838-842, 2010

12 DECODE Study Group, "Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria" 161 : 397-405, 2001

13 "Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III)" 285 : 2486-2497, 2001

14 Heine RJ, "Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial" 143 : 559-569, 2005

15 Kohnert KD, "Evaluation of the mean absolute glucose change as a measure of glycemic variability using continuous glucose monitoring data" 15 : 448-454, 2013

16 Raz I, "Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial" 32 : 381-386, 2009

17 Wang JS, "Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison" 33 : 1932-1942, 2011

18 Yamazaki M, "Effect of repaglinide versus glimepiride on daily blood glucose variability and changes in blood inflammatory and oxidative stress markers" 6 : 54-, 2014

19 Holman RR, "Effect of nateglinide on the incidence of diabetes and cardiovascular events" 362 : 1463-1476, 2010

20 Bradescu OM, "Correlates of the diurnal plasma glucose variability in non-insulin-treated type 2 diabetic patients" 1 : 53-58, 2008

21 Guerci B, "Continuous glucose profiles with vildagliptin versus sitagliptin in add-on to metformin: results from the randomized Optima study" 38 : 359-366, 2012

22 Jin SM, "Clinical factors associated with absolute and relative measures of glycemic variability determined by continuous glucose monitoring: an analysis of 480 subjects" 104 : 266-272, 2014

23 Brownlee M, "Biochemistry and molecular cell biology of diabetic complications" 414 : 813-820, 2001

24 Stratton IM, "Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study" 321 : 405-412, 2000

25 Chiasson JL, "Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance : the STOP-NIDDM trial" 290 : 486-494, 2003

26 Siegelaar SE, "A decrease in glucose variability does not reduce cardiovascular event rates in type 2 diabetic patients after acute myocardial infarction: a reanalysis of the HEART2D study" 34 : 855-857, 2011

27 Andrus B, "2013 ACC/AHA guideline on the assessment of cardiovascular risk" 63 (63): 2886-, 2014