Epidemiological and Clinical Studies on Insulin Resistance and Diabetes

Abstract

In Uppsala, extensive epidemiological and clinical studies on insulin resistance and diabetes have been ongoing for the past 30 years. A prospective cohort study of men born 1920-24, living in Uppsala County, was initiated during 1969-74 (the Uppsala Longitudinal Study of Adult Men, ULSAM). Risk factors for cardiovascular disease were examined in 2,322 men, and re-examinations have been performed every 10 years. At the first follow-up, when the men were 60 years old, insulin resistance was found to be a risk factor for development of hypertension and diabetes. In addition, treatment with antihypertensive medication was an independent risk factor for development of diabetes. These findings resulted in a series of clinical studies on metabolic effects of antihypertensive agents. At the second follow-up, when the men were 70 years old, the development of hypertension and diabetes was once again in focus, but at this time, cross-sectional and prospective studies of other cardiovascular determinants, such as circadian blood pressure pattern, left ventricular geometry and function, muscle morphology, ion status, fibrinolysis and cognitive function, were also performed. The cohort has furthermore been linked to the Swedish census and hospital discharge and cause of death registries, it has been used for studies on relationships between birth weight and cardiovascular disease, and genetic analyses have been performed, taking advantage of the long observation time obtained in this cohort. The cohort is currently being re-examined for the third time, and will hopefully continue to provide valuable information on the epidemiology of diabetes and cardiovascular disease in the future.

Fasting Serum C‐Peptide Levels Predict Cardiovascular and Overall Death in Nondiabetic Adults

“…Substantial evidence supports the role of insulin resistance in the development of type 2 diabetes, but a relationship between insulin resistance‐hyperinsulinemia as measured by C‐peptide levels in adults without diabetes and a future cardiovascular death has not been established from our literature review. This association remained significant for adults without clinical manifestations of insulin resistance such as those with normal fasting glucose levels or without metabolic syndrome at the time of C‐peptide level testing.…”

Proinsulin and acute insulin response independently predict Type 2 diabetes mellitus in men—report from 27 years of follow-up study

“…The outcome variables, described below, were defined using the follow-up data from the second, third and fourth investigations (U-60, U-70 and U-77) carried out in the original Uppsala-cohort at age 60 years (U-60) between 1980 and 1984 (1860 subjects participated) [21], at age 70 years (U-70) between 1991 and 1995 (1221 out of 1681 eligible men participated) [22] and at age 77 years (U-77) between 1998 and 2001 (839 out of 1079 eligible men participated). Type 2 diabetes was defined according to the World Health Organisation (WHO) criteria from 1999 [23] (using fasting concentrations) and/or use of OHAs.…”

The Uppsala studies on developmental origins of health and disease

“…This possibility to advance the understanding of life‐course origins of cardiovascular and other diseases was recognized by a team of Swedish and UK researchers: Hans Lithell, David Leon, Paul McKeigue, and Denny Vågerö. Under the leadership of this group, several large‐scale epidemiological studies on developmental origins of health have been initiated in Uppsala to date [28–30].…”