Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study

Tabák, Ádám G.; Jokela, Markus; Akbaraly, Tasnime; Brunner, Eric J.; Kivimäki, Mika; Witte, Daniel R.

doi:10.1016/s0140-6736(09)60619-x

Cited by 759 publications

(691 citation statements)

References 43 publications

(80 reference statements)

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“…Although it could not be examined with our data, we speculate that the recent reduction in the proportion of adults with very low HbA 1c values may be due to persons spending a smaller proportion of their time in the fasting state than in the previous decade. These findings suggest that FI level may be more sensitive to lifestyle or environmental changes than HbA 1c or FPG levels and thus possibly an earlier indicator of diabetogenic trends in the population [6]. Our finding that the estimated increase in FI level disappeared after adjustment for BMI or waist circumference suggests that this increase was associated with the increasing adiposity of the US population.…”

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

“…Persons who eventually develop type 2 diabetes do not typically have increased FPG until within 2 years prior to diagnosis [6]. However, their 2 h post-challenge glucose level increases approximately 5 years prior to diagnosis [6,7]. Thus, in the earlier years prior to diagnosis, the underlying pathophysiological processes that eventually lead to type 2 diabetes are hidden by homeostatic mechanisms that tend to preserve normal levels of fasting or post-challenge glycaemia.…”

Section: Discussionmentioning

confidence: 99%

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Recent population changes in HbA1c and fasting insulin concentrations among US adults with preserved glucose homeostasis

et al. 2010

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Aims/hypothesis Although diagnosed type 2 diabetes has increased in the past decade, little is known about accompanying changes in fasting plasma glucose (FPG), HbA 1c and fasting serum insulin (FI) levels in the nondiabetic population. Methods Using population estimates from National Health and Nutrition Examination Surveys, we compared distribution of FPG, HbA 1c and FI in non-diabetic US persons who were ≥20 years old in 1999 to 2006 with that in persons of the same age in 1988 to 1994. Results Age-, sex-and race-adjusted mean FPG levels between the two study periods did not change, but mean HbA 1c and FI levels increased (0.10% and 4.8 pmol/l, respectively; p<0.001 for both). The increased HbA 1c level was driven largely by an upward shift in the lower end of the HbA 1c distribution. In contrast, the increased FI level was driven primarily by an upward shift in the middle and higher end of FI distribution, especially among persons aged 20 to 44 years. After adjustments for BMI or waist circumference, the increase in the mean HbA 1c level was attenuated (0.06%; p<0.001), whereas the mean FPG level decreased by 0.1 mmol/l (p<0.001) and the mean FI level no longer demonstrated significant change.Conclusions/interpretation Despite little change in the distribution of FPG levels, HbA 1c and FI levels increased in the non-diabetic population in the past decade. The increase in FI levels suggests that levels of insulin resistance were greater among US adults, especially young adults, than in the previous decade.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Recent population changes in HbA1c and fasting insulin concentrations among US adults with preserved glucose homeostasis

et al. 2010

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“…2007; Tabak et al. 2009). From a public health standpoint, physical activity is central to both the prevention and treatment of T2D, yet the exact mechanisms for this effect remain imperfectly understood.…”

Section: Introductionmentioning

confidence: 99%

Exercise training prevents skeletal muscle plasma membrane cholesterol accumulation, cortical actin filament loss, and insulin resistance in C57BL/6J mice fed a western-style high-fat diet

et al. 2017

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Insulin action and glucose disposal are enhanced by exercise, yet the mechanisms involved remain imperfectly understood. While the causes of skeletal muscle insulin resistance also remain poorly understood, new evidence suggest excess plasma membrane (PM) cholesterol may contribute by damaging the cortical filamentous actin (F‐actin) structure essential for GLUT4 glucose transporter redistribution to the PM upon insulin stimulation. Here, we investigated whether PM cholesterol toxicity was mitigated by exercise. Male C57BL/6J mice were placed on low‐fat (LF, 10% kCal) or high‐fat (HF, 45% kCal) diets for a total of 8 weeks. During the last 3 weeks of this LF/HF diet intervention, all mice were familiarized with a treadmill for 1 week and then either sham‐exercised (0 m/min, 10% grade, 50 min) or exercised (13.5 m/min, 10% grade, 50 min) daily for 2 weeks. HF‐feeding induced a significant gain in body mass by 3 weeks. Sham or chronic exercise did not affect food consumption, water intake, or body mass gain. Prior to sham and chronic exercise, “pre‐intervention” glucose tolerance tests were performed on all animals and demonstrated that HF‐fed mice were glucose intolerant. While sham exercise did not affect glucose tolerance in the LF or HF mice, exercised mice showed an improvement in glucose tolerance. Muscle from sham‐exercised HF‐fed mice showed a significant increase in PM cholesterol, loss of cortical F‐actin, and decrease in insulin‐stimulated glucose transport compared to sham‐exercised LF‐fed mice. These HF‐fed skeletal muscle membrane/cytoskeletal abnormalities and insulin resistance were improved in exercised mice. These data reveal a new therapeutic aspect of exercise being regulation of skeletal muscle PM cholesterol homeostasis. Further studies on this mechanism of insulin resistance and the benefits of exercise on its prevention are needed.

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“…On the other hand, hypoglycemia or rapid changes in plasma glucose may lead to elevations of counterregulatory hormones, such as epinephrine and norepinephrine, and these increases induce vasoconstriction and platelet aggregation 3, 15. Furthermore, there is evidence that rapidly increasing glucose concentrations, rather than gradual increases, occur late in diabetes mellitus,16, 17 and individuals with stable FPG concentrations are less likely to develop diabetes mellitus. The “ticking clock” hypothesis proposed by Haffner et al18 claims that the plasma glucose level should be treated as a continuous variable, and different trajectories of FPG can reflect both the FPG level and the changing pattern simultaneously.…”

Section: Discussionmentioning

confidence: 99%

Trajectories of Long‐Term Normal Fasting Plasma Glucose and Risk of Coronary Heart Disease: A Prospective Cohort Study

Yuan

Yang

Wang

et al. 2018

JAHA

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BackgroundFasting plasma glucose (FPG) levels can vary over time and its longitudinal changing patterns may predict cardiometabolic risk. We aim to identify different trajectories of FPG in those who remained normoglycemic and investigate the association between trajectory groups and coronary heart disease risk in a large prospective cohort study.Methods and ResultsA total of 20 514 subjects between ages 20 and 80 years were included at baseline. All participants had maintained normal FPG throughout an average follow‐up period of 5.8 years. We identified 3 distinct trajectories using a group‐based trajectory model, labeled by initial value and changing pattern: low‐increasing (n=12 694), high‐increasing‐decreasing (n=5330), and high‐decreasing‐increasing (n=2490). The coronary heart disease incidence density among these 3 groups (3.00, 4.05, and 3.26 per 1000 person‐years, respectively) was significantly different (P=0.038). The high‐increasing‐decreasing group was characterized by a starting FPG of 4.80 mmol/L, and increased up to 5.42 mmol/L at age 55, then decreased thereafter. Treating the low‐increasing group as the reference, the age‐ and sex‐adjusted hazard ratio was 1.58 (95% confidence interval, 1.23–2.02) for the high‐increasing‐decreasing group by Cox proportional hazard regression. After adjustment for other potential confounding factors, the hazard ratio is 1.40 (95% confidence interval, 1.08–1.81). The association persisted after adjustment for baseline FPG, mean, or SD of FPG.ConclusionsDistinct trajectories of long‐term normal FPG are associated with the development of coronary heart disease, which is independent of other metabolic factors including FPG levels. These findings have implications for intervention and prevention of coronary heart disease among individuals who are normoglycemic.

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Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study

Abstract: Background-Little is known about the timing of changes in glucose metabolism prior to type 2 diabetes development. We aimed to characterize trajectories of fasting and postload glucose, insulin sensitivity and insulin secretion in individuals developing type 2 diabetes.

Cited by 759 publications

References 43 publications

Recent population changes in HbA1c and fasting insulin concentrations among US adults with preserved glucose homeostasis

Recent population changes in HbA1c and fasting insulin concentrations among US adults with preserved glucose homeostasis

Exercise training prevents skeletal muscle plasma membrane cholesterol accumulation, cortical actin filament loss, and insulin resistance in C57BL/6J mice fed a western-style high-fat diet

Trajectories of Long‐Term Normal Fasting Plasma Glucose and Risk of Coronary Heart Disease: A Prospective Cohort Study

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