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Trends in obesity and type 2 diabetes: ethnic aspects and links to adipokines
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Objective The prevalence of obesity and related diseases such as type 2 diabetes mellitus (T2DM) is increasing worldwide, and the Asian Indian population seems to be particularly susceptible to developing T2DM, even at a low body mass index (BMI). In Sweden, the age-adjusted prevalence of diabetes has not increased despite increasing self-reported obesity. However, modern data on the prevalence of obesity and T2DM in Scandinavia are absent.The biochemical links between obesity and subsequent T2DM are unknown, but the adipocyte-derived hormones leptin and adiponectin (adipokines) have been suggested as potential links because they both are related to insulin and glucose physiology. Some studies have found leptin to be an independent predictor of T2DM in men but not in women, although these results are inconsistent. In contrast, adiponectin has more consistently been linked to development of T2DM in both men and women. Furthermore, the leptin–adiponectin ratio may predict incident T2DM better than either of the two hormones separately.The aims of this thesis were to describe time trends in obesity and T2DM in northern Sweden, to evaluate leptin and adiponectin as predictors of deterioration in glucose metabolism including T2DM, and to evaluate leptin as a risk marker regarding ethnic differences, circ-annual variation, and intra-individual stability.

Materials and methods Three large population surveys were used, the Northern Sweden MONICA (MONitoring of Trends and Determinants in CArdiovascular Disease) study, the Västerbotten Intervention Programme (VIP), and the Mauritius Non-Communicable Disease Study. Within the MONICA study, six cross-sectional surveys were performed in Sweden’s two northernmost counties, Norrbotten and Västerbotten, between 1986 and 2009. A total of 1000 men and 1000 women ages 25–64 years, also including from 1994 250 men and 250 women ages 65–74 years, were independently chosen for each survey. The overall participation rate was 75%. In 1999, a reinvestigation was performed in 74% of all participants from the three first surveys. Data from the MONICA surveys were used in papers I and IV and data from the reinvestigation survey in paper II. VIP is an ongoing population intervention program that started in the mid-eighties targeting cardiovascular risk factors and has covered the whole county of Västerbotten since 1991. Inhabitants are invited the years they turn 40, 50, and 60 years old, and the annual participation rate has varied between 48% and 67%. A subset (n=1780) from VIP was used in paper II for the circ-annual leptin analysis, and VIP data linked to the diabetes register in Västerbotten (DiabNorr) were used in a case referent study (640 patients with T2DM) in paper III. The Mauritius Non-Communicable Disease Study was performed in 1987 in 10 randomly selected (with probability proportional to size) population clusters. All eligible adults ages 25–74 years were invited, and the participation rate was 86% (n=5083). In 1992, a follow-up survey was performed in 49% of the initial participants. The Mauritius survey data were used in paper II.

Results

I. BMI increased in men ages 25–74 years and in women ages 25–44 years in northern Sweden between 1986 and 2004. The prevalence of obesity (BMI 30) increased in men ages 25–44 and 55–74 years and in women ages 25–44 years. The prevalence of obesity increased from 10.4% to 19.1% in men and from 12.9% to 17.9% in women ages 25–64 years. Waist circumference (WC) decreased in women of all ages and in men ages 55–64 years between 1986 and 1990. After 1990, WC increased again, and the prevalence of abdominal obesity rose markedly in women ages 25–64 years.

II. Differences in circulating levels of leptin, leptin per BMI unit (leptin/BMI), and leptin per cm in WC (leptin/waist) were tested in men and women of Asian Indian, Creole (African), and Caucasian ethnicity. Asian Indian men and women had the highest leptin concentrations and Caucasian men and women the lowest while Creole men and women had intermediate values for leptin, leptin/BMI, and leptin/waist. No circ-annual variation in leptin concentrations was seen in Caucasians. The intra-individual test– retest stability for leptin was equal in men and women of different ethnicities, over 5–13 years, with an intra-class correlation of 0.65–0.82.

III. High adiponectin concentrations predicted decreased risk of T2DM in both insulin-sensitive and insulin-resistant men and women, whereas high leptin levels predicted increased risk for T2DM only in insulinsensitive men. A high leptin–adiponectin ratio predicted T2DM in both men and women, and men with a high ratio had a shorter time to diagnosis than those with a low ratio.

IV. In northern Sweden, fasting and post-load glucose increased in women ages 24–65 years with 0.2 mmol/l and 0.7 mmol/l, respectively, between 1990 and 2009. Consequently, the prevalence of impaired fasting glucose and impaired glucose tolerance (IGT) rose from 4.5% to 7.7%, and from 7.8% to 14.5%, respectively. In men, post-load glucose increased at 0.5 mmol/l, and the prevalence of IGT rose from 3.5% to 10.1%. The prevalence of diabetes did not increase. An independent relationship between leptin and changes in fasting and post-load glucose was seen in men but not in women.

Conclusion An increasing obesity and concomitant deterioration in glucose metabolism was seen in northern Sweden in the period studied. High adiponectin concentrations predicted a decreased risk of T2DM in both men and women, whereas high leptin concentrations predicted an increase in fasting and post-load glucose as well as an increased risk of T2DM in men but not in women. Individual insulin resistance status modified the association between leptin and T2DM, and the leptin–adiponectin ratio may add further predictive information beyond the measures of the separate hormones. In relation to traditional anthropometric measures of obesity, Asian Indian men and women had the highest and Caucasians the lowest concentrations of leptin while Creole (African) men and women had intermediate levels. As a risk marker, leptin has a high intra-individual stability, equal in men and women and among different ethnicities over 5–13 years with no circ-annual variation.

Place, publisher, year, edition, pages
Umeå: Umeå University , 2011. , 83 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1449
Keyword [en]
Type 2 diabetes, leptin, adiponectin, obesity, abdominal obesity, epidemiology, ethnicity, fasting glucose, post-load glucose
National Category
Medical and Health Sciences
Research subject
Family Medicine
Identifiers
URN: urn:nbn:se:umu:diva-49398ISBN: 978-91-7459-276-4 (print)OAI: oai:DiVA.org:umu-49398DiVA: diva2:455710
Public defence
2011-12-09, Sal 933, NUS, Umeå, 10:00 (Swedish)
Opponent
Supervisors
Available from: 2011-11-18 Created: 2011-11-10 Last updated: 2011-11-18Bibliographically approved
List of papers
1. Trends in obesity and its distribution: data from the Northern Sweden MONICA survey, 1986–2004
Open this publication in new window or tab >>Trends in obesity and its distribution: data from the Northern Sweden MONICA survey, 1986–2004
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2008 (English)In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 16, no 5, 1120-1128 p.Article in journal (Refereed) Published
Abstract [en]

Objective: Obesity, especially abdominal, is a risk factor for many diseases. This study explored trends in theprevalence of general and abdominal obesity, 1986–2004, in northern Sweden.

Methods and Procedures: Cross-sectional population surveys were performed in 1986, 1990, 1994, 1999, and 2004;250 men and 250 women aged 25−34, 35−44, 45−54, and 55−64 years (from 1994, also 65−74 years) were randomlyselected; the overall participation rate was 77%. Anthropometric data were used.

Results: Weight and BMI increased in all men, most significantly in men aged 25−64 years (P < 0.0005). Weightincreased in women aged 25−64 years (P < 0.005) and BMI in women aged 25−44 years (P < 0.005). Prevalence ofobesity (BMI≥ 30) increased significantly in men aged 25−44 and 55−74 years (P < 0.005; for men 65−74 years old,P< 0.05) and in women aged 25−44 years (P < 0.005). Waist circumference decreased significantly between 1986and 1990 in all women (P < 0.005) and in men aged 55−64 years (P < 0.05). After 1990 waist circumference increased, most markedly so in women; by 2004 circumference measurements for women, and for men aged 55−64 years, were equal to those of 1986, while for men aged 25−54 years they were higher. Prevalence of abdominal obesity has increased since 1990, most markedly so in women aged 45−64 years (P < 0.0005).

Discussion: The rapid increase in both general and central obesity raises concern for the future; increasing abdominalobesity in women is particularly alarming.

Keyword
abdominal adiposity, trends, waist circumference, obesity
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-49377 (URN)10.1038/oby.2008.8 (DOI)
Available from: 2011-11-15 Created: 2011-11-10 Last updated: 2017-12-08Bibliographically approved
2. Higher leptin levels in Asian Indians than Creoles and Europids:  a potential explanation for increased metabolic risk
Open this publication in new window or tab >>Higher leptin levels in Asian Indians than Creoles and Europids:  a potential explanation for increased metabolic risk
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2010 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 34, no 5, 878-885 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE:

Leptin predicts cardiovascular diseases and type 2 diabetes, diseases to which Asian Indians are highly susceptible. As a risk marker, leptin's intra-individual and seasonal stability is unstudied and only small studies have compared leptin levels in Asian Indians with other populations. The aim of this study was to explore ethnicity related differences in leptin levels and its intra-individual and seasonal stability.

METHODS:

Leptin and anthropometric data from the northern Sweden MONICA (3513 Europids) and the Mauritius Non-communicable Disease (2480 Asian Indians and Creoles) studies were used. In both studies men and women, 25- to 74-year old, participated in both an initial population survey and a follow-up after 5-13 years. For the analysis of seasonal leptin variation, a subset of 1780 participants, 30- to 60-year old, in the Västerbotten Intervention Project was used.

RESULTS:

Asian Indian men and women had higher levels of leptin, leptin per body mass index (BMI) unit (leptin/BMI) or per cm in waist circumference (WC; leptin/waist) than Creoles and Europids when adjusted for BMI (all P<0.0005) or WC (all P<0.005). In men, Creoles had higher leptin, leptin/BMI and leptin/waist than Europids when adjusted for BMI or WC (all P<0.0005). In women, Creoles had higher leptin/BMI and leptin/waist than Europids only when adjusted for WC (P<0.0005). Asian Indian ethnicity in both sexes, and Creole ethnicity in men, was independently associated with high leptin levels. The intra-class correlation for leptin was similar (0.6-0.7), independently of sex, ethnicity or follow-up time. No seasonal variation in leptin levels was seen.

CONCLUSION:

Asian Indians have higher levels of leptin, leptin/BMI and leptin/waist than Creoles and Europids. Leptin has a high intra-individual stability and seasonal leptin variation does not appear to explain the ethnic differences observed here

Keyword
leptin, ethnicity, season, intra-individual stability
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-49380 (URN)10.1038/ijo.2010.19 (DOI)000277435700011 ()
Available from: 2011-11-15 Created: 2011-11-10 Last updated: 2017-12-08Bibliographically approved
3. The impact of leptin and adiponectin on incident type 2 diabetes is modified by sex and insulin resistance
Open this publication in new window or tab >>The impact of leptin and adiponectin on incident type 2 diabetes is modified by sex and insulin resistance
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background Adiponectin and leptin and their ratio have been associated with incident type 2 diabetes (T2DM), although presented data are conflicting and populations studied have been small. In this large prospective nested case referent study, we hypothesised that these associations are sex-specific and may be modified by insulin resistance.

Methods Men and women aged 30–60 years with incident T2DM (n=640) and a prior health survey within the Västerbotten Intervention Programme (VIP), and matched referents (n=1564) were identified. Using conditional logistic regression analyses, we tested whether baseline plasma adiponectin and leptin levels and their ratio independently predicted incident T2DM, stratified for gender and insulin resistance.

Results Adjusted for traditional risk factors, fourth-quartile levels of adiponectin were associated with a reduced risk of T2DM in men (OR 0.55 [0.36–0.86]) and women (OR 0.47 [0.27–0.83]). Quartile four of the leptin/adiponectin ratio predicted T2DM in both men (OR 3.08 [1.68–5.67]) and women (OR 3.31 [1.56–7.03]), while quartile-four levels of leptin predicted T2DM only in men (OR 2.30 [1.32–4.02]). When stratified for insulin sensitivity and adjusted for BMI, loge-transformed leptin predicted T2DM in insulin-sensitive men (OR 1.56 [1.13–2.17]) but not in insulin-resistant men (OR 1.03 [0.76–1.39]). The effect of adiponectin and the leptin/adiponectin ratio was not influenced by the insulin sensitivity status.

Conclusions Leptin in men and adiponectin in both sexes were independent predictors of T2DM. The association was modified by the degree of insulin sensitivity. The leptin/adiponectin ratio may add predictive information beyond the separate hormones

Keyword
adiponectin, leptin, leptin/adiponectin ratio, diabetes mellitus, insulin resistance
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-49381 (URN)
Available from: 2011-11-10 Created: 2011-11-10 Last updated: 2015-04-29Bibliographically approved
4. A right-hand shift of the distribution of fasting and post load glucose in northern Sweden between 1990 and 2009, and its predictors
Open this publication in new window or tab >>A right-hand shift of the distribution of fasting and post load glucose in northern Sweden between 1990 and 2009, and its predictors
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background Recent Swedish studies have shown stable diabetes prevalence despite increasing obesity, but glucose levels may shift upwards below the diagnostic threshold for diabetes. Determinants for this shift are not consistently described, and may include obesity and obesity related factors such as the adipokine leptin.

Aims To explore secular trends in diabetes prevalence, glucose concentrations and glucose intolerance in northern Sweden, to evaluate if these trends are uniformly distributed throughout the spectrum of glucose concentrations, and to relate trends in glucose concentrations to  traditional risk factors and leptin.

Methods Four cross-sectional population surveys between 1990 and 2009 with 7069 participants aged 25-64 years with an overall participation rate of 74.4%. Tukey mean-difference plot were used to examine changes in glucose distribution together with trend analyses in each decile of glucose distribution. Linear regression was used to estimate changes in glucose levels in relation to survey year and risk factors including leptin.

Results Fasting and post load glucose in women (all p<0.001) and post load glucose in men (p=0.004) increased, and the increase was seen in almost all deciles of glucose concentrations, but more pronounced in the upper deciles. In men, fasting glucose remained unchanged, though with an increase in lower deciles. The prevalence of impaired glucose tolerance rose in women from 7.8 to 14.5% and in men from 3.5 to 10.1% (all p=0.004), and the prevalence of impaired fasting glucose rose in women from 4.5 to 7.7% (p<0.001), but was unchanged in men.  The prevalence of diabetes did not change and was 2009 in men 6.4%, and in women 6.5%.  Leptin could, on top of traditional risk factors, in men partly explain the variance in fasting (p=0.008) and post load (p<0.001) glucose. 

Conclusion The prevalence of diabetes did not increase in northern Sweden between 1986 and 2009, despite increasing fasting and post load glucose levels seen in most deciles of glucose distribution. Leptin is significantly associated with changes in fasting and post load glucose in men.

Keyword
diabetes mellitus type 2, IFG, IGT, post load glucose, fasting glucose, leptin, prevalence, time trend, Northern Sweden MONICA
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-49382 (URN)
Available from: 2011-11-10 Created: 2011-11-10 Last updated: 2011-11-18Bibliographically approved

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