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Patterns of obesity development before the diagnosis of type 2 diabetes: the Whitehall II cohort study.

Vistisen D, Witte DR, Tabák AG, Herder C, Brunner EJ, Kivimäki M, Færch K - PLoS Med. (2014)

Bottom Line: Since the generalizability of these findings is limited, the results need confirmation in other study populations.While these results should be verified independently, the great majority of patients had modest weight gain prior to diagnosis.These results suggest that strategies focusing on small weight reductions for the entire population may be more beneficial than predominantly focusing on weight loss for high-risk individuals.

View Article: PubMed Central - PubMed

Affiliation: Steno Diabetes Center, Gentofte, Denmark.

ABSTRACT

Background: Patients with type 2 diabetes vary greatly with respect to degree of obesity at time of diagnosis. To address the heterogeneity of type 2 diabetes, we characterised patterns of change in body mass index (BMI) and other cardiometabolic risk factors before type 2 diabetes diagnosis.

Methods and findings: We studied 6,705 participants from the Whitehall II study, an observational prospective cohort study of civil servants based in London. White men and women, initially free of diabetes, were followed with 5-yearly clinical examinations from 1991-2009 for a median of 14.1 years (interquartile range [IQR]: 8.7-16.2 years). Type 2 diabetes developed in 645 (1,209 person-examinations) and 6,060 remained free of diabetes during follow-up (14,060 person-examinations). Latent class trajectory analysis of incident diabetes cases was used to identify patterns of pre-disease BMI. Associated trajectories of cardiometabolic risk factors were studied using adjusted mixed-effects models. Three patterns of BMI changes were identified. Most participants belonged to the "stable overweight" group (n = 604, 94%) with a relatively constant BMI level within the overweight category throughout follow-up. They experienced slightly worsening of beta cell function and insulin sensitivity from 5 years prior to diagnosis. A small group of "progressive weight gainers" (n = 15) exhibited a pattern of consistent weight gain before diagnosis. Linear increases in blood pressure and an exponential increase in insulin resistance a few years before diagnosis accompanied the weight gain. The "persistently obese" (n = 26) were severely obese throughout the whole 18 years before diabetes diagnosis. They experienced an initial beta cell compensation followed by loss of beta cell function, whereas insulin sensitivity was relatively stable. Since the generalizability of these findings is limited, the results need confirmation in other study populations.

Conclusions: Three patterns of obesity changes prior to diabetes diagnosis were accompanied by distinct trajectories of insulin resistance and other cardiometabolic risk factors in a white, British population. While these results should be verified independently, the great majority of patients had modest weight gain prior to diagnosis. These results suggest that strategies focusing on small weight reductions for the entire population may be more beneficial than predominantly focusing on weight loss for high-risk individuals.

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Trajectories for a hypothetical male, not on lipid-lowering treatment, age 60 years at time 0 of total cholesterol (A), HDL cholesterol (B), LDL cholesterol (C), and triglycerides (D) from 18 years before time of diagnosis/last examination.Solid lines indicate estimated trajectories for each group and dashed lines are 95% confidence limits. Black bars at the bottom indicate the relative data distribution over the follow-up period. Light blue, stable overweight; dark blue, progressive weight gain; red, persistently obese; grey, diabetes-free population.
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pmed-1001602-g003: Trajectories for a hypothetical male, not on lipid-lowering treatment, age 60 years at time 0 of total cholesterol (A), HDL cholesterol (B), LDL cholesterol (C), and triglycerides (D) from 18 years before time of diagnosis/last examination.Solid lines indicate estimated trajectories for each group and dashed lines are 95% confidence limits. Black bars at the bottom indicate the relative data distribution over the follow-up period. Light blue, stable overweight; dark blue, progressive weight gain; red, persistently obese; grey, diabetes-free population.

Mentions: Trajectories of diastolic blood pressure did not differ between the progressive weight gainers and the persistently obese groups (Figure 2D, p = 0.18). Individuals with stable overweight exhibited near-normal diastolic blood pressure during follow-up (Figure 2D, p<0.001 versus progressive weight gainers, p = 0.04 versus persistently obese), although systolic blood pressure did not differ significantly between the groups (Figure 2C, p≥0.17). Plasma lipid levels showed a stable pattern towards diabetes diagnosis in the stable overweight group (Figure 3A–3D). LDL cholesterol levels were lower among the progressive weight gainers than among the group of stable overweight (Figure 3C, p = 0.010). The progressive weight gainers did not differ from the other groups with respect to other blood lipids (Figure 3, p≥0.07 for all). HDL cholesterol was significantly lower during follow-up in the persistently obese compared with the stable overweight group (Figure 3B, p = 0.03), whereas triglyceride levels were higher (Figure 3D, p = 0.003).


Patterns of obesity development before the diagnosis of type 2 diabetes: the Whitehall II cohort study.

Vistisen D, Witte DR, Tabák AG, Herder C, Brunner EJ, Kivimäki M, Færch K - PLoS Med. (2014)

Trajectories for a hypothetical male, not on lipid-lowering treatment, age 60 years at time 0 of total cholesterol (A), HDL cholesterol (B), LDL cholesterol (C), and triglycerides (D) from 18 years before time of diagnosis/last examination.Solid lines indicate estimated trajectories for each group and dashed lines are 95% confidence limits. Black bars at the bottom indicate the relative data distribution over the follow-up period. Light blue, stable overweight; dark blue, progressive weight gain; red, persistently obese; grey, diabetes-free population.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921118&req=5

pmed-1001602-g003: Trajectories for a hypothetical male, not on lipid-lowering treatment, age 60 years at time 0 of total cholesterol (A), HDL cholesterol (B), LDL cholesterol (C), and triglycerides (D) from 18 years before time of diagnosis/last examination.Solid lines indicate estimated trajectories for each group and dashed lines are 95% confidence limits. Black bars at the bottom indicate the relative data distribution over the follow-up period. Light blue, stable overweight; dark blue, progressive weight gain; red, persistently obese; grey, diabetes-free population.
Mentions: Trajectories of diastolic blood pressure did not differ between the progressive weight gainers and the persistently obese groups (Figure 2D, p = 0.18). Individuals with stable overweight exhibited near-normal diastolic blood pressure during follow-up (Figure 2D, p<0.001 versus progressive weight gainers, p = 0.04 versus persistently obese), although systolic blood pressure did not differ significantly between the groups (Figure 2C, p≥0.17). Plasma lipid levels showed a stable pattern towards diabetes diagnosis in the stable overweight group (Figure 3A–3D). LDL cholesterol levels were lower among the progressive weight gainers than among the group of stable overweight (Figure 3C, p = 0.010). The progressive weight gainers did not differ from the other groups with respect to other blood lipids (Figure 3, p≥0.07 for all). HDL cholesterol was significantly lower during follow-up in the persistently obese compared with the stable overweight group (Figure 3B, p = 0.03), whereas triglyceride levels were higher (Figure 3D, p = 0.003).

Bottom Line: Since the generalizability of these findings is limited, the results need confirmation in other study populations.While these results should be verified independently, the great majority of patients had modest weight gain prior to diagnosis.These results suggest that strategies focusing on small weight reductions for the entire population may be more beneficial than predominantly focusing on weight loss for high-risk individuals.

View Article: PubMed Central - PubMed

Affiliation: Steno Diabetes Center, Gentofte, Denmark.

ABSTRACT

Background: Patients with type 2 diabetes vary greatly with respect to degree of obesity at time of diagnosis. To address the heterogeneity of type 2 diabetes, we characterised patterns of change in body mass index (BMI) and other cardiometabolic risk factors before type 2 diabetes diagnosis.

Methods and findings: We studied 6,705 participants from the Whitehall II study, an observational prospective cohort study of civil servants based in London. White men and women, initially free of diabetes, were followed with 5-yearly clinical examinations from 1991-2009 for a median of 14.1 years (interquartile range [IQR]: 8.7-16.2 years). Type 2 diabetes developed in 645 (1,209 person-examinations) and 6,060 remained free of diabetes during follow-up (14,060 person-examinations). Latent class trajectory analysis of incident diabetes cases was used to identify patterns of pre-disease BMI. Associated trajectories of cardiometabolic risk factors were studied using adjusted mixed-effects models. Three patterns of BMI changes were identified. Most participants belonged to the "stable overweight" group (n = 604, 94%) with a relatively constant BMI level within the overweight category throughout follow-up. They experienced slightly worsening of beta cell function and insulin sensitivity from 5 years prior to diagnosis. A small group of "progressive weight gainers" (n = 15) exhibited a pattern of consistent weight gain before diagnosis. Linear increases in blood pressure and an exponential increase in insulin resistance a few years before diagnosis accompanied the weight gain. The "persistently obese" (n = 26) were severely obese throughout the whole 18 years before diabetes diagnosis. They experienced an initial beta cell compensation followed by loss of beta cell function, whereas insulin sensitivity was relatively stable. Since the generalizability of these findings is limited, the results need confirmation in other study populations.

Conclusions: Three patterns of obesity changes prior to diabetes diagnosis were accompanied by distinct trajectories of insulin resistance and other cardiometabolic risk factors in a white, British population. While these results should be verified independently, the great majority of patients had modest weight gain prior to diagnosis. These results suggest that strategies focusing on small weight reductions for the entire population may be more beneficial than predominantly focusing on weight loss for high-risk individuals.

Show MeSH
Related in: MedlinePlus