Effect of progression from impaired glucose tolerance to diabetes on cardiovascular risk factors and its amelioration by lifestyle and metformin intervention: the Diabetes Prevention Program randomized trial by the Diabetes Prevention Program Research Group.
OBJECTIVE
Although subjects with diabetes have increased risk for cardiovascular disease (CVD), the evolution of this increased risk as pre-diabetic individuals progress to diabetes is not understood. This study examines the longitudinal relationship between selected CVD risk factors (blood pressure, triglycerides, HDL and LDL cholesterol, and LDL peak particle density [PPD]) and glycemia in the three treatment groups of the Diabetes Prevention Program.


METHODS
A total of 3,234 participants with impaired glucose tolerance (IGT) were followed for a mean of 3.2 years after randomization to intensive lifestyle intervention (ILS), metformin, or placebo. Using repeated-measures models, adjusted mean levels of risk factors were estimated for an annual change in glycemic status. Tests were also conducted to assess the risk factor trends with improvement or worsening of glycemic status.


RESULTS
CVD risk factor values and changes from baseline became more unfavorable as glucose tolerance status deteriorated but improved with reversion to normal glucose tolerance (NGT), especially in the ILS intervention group (trend test P < 0.001 for all risk factors except for LDL PPD [P = 0.02] in ILS and HDL cholesterol [P = 0.02] in placebo). Although there were few significant differences in the transition from IGT to diabetes, there were strong relationships between risk factors and continuous measures of glycemia.


CONCLUSIONS
Progression from IGT to diabetes is associated with mild deterioration, whereas reversion to NGT is associated with improvement in risk factors. Early intervention with ILS, but less so with metformin, in participants at high risk for diabetes improves the cardiovascular risk and glucose tolerance profile simultaneously.
Goldberg
Ronald B
RB
Diabetes Prevention Program Coordinating Center, George Washington University, Rockville, Maryland, USA.
Temprosa
Marinella
M
Haffner
Steven
S
Orchard
Trevor J
TJ
Ratner
Robert E
RE
Fowler
Sarah E
SE
Mather
Kieren
K
Marcovina
Santica
S
Saudek
Chris
C
Matulik
Margaret J
MJ
Price
David
D
D000328:Adult; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000517:prevention & control; D048909:Diabetes Complications / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology*; D003925:Diabetic Angiopathies / Q000453:epidemiology* / Q000517:prevention & control; D018450:Disease Progression; D005006:Ethnicity; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008019:Life Style; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D044469:Racial Groups; D012307:Risk Factors
D007004:Hypoglycemic Agents; D008055:Lipids; D010919:Placebos; D008687:Metformin