Resolution of Fatty Liver and Risk of Incident Diabetes

Context: Fatty liver is associated with an increased risk of type 2 diabetes, but whether an increased risk remains in people in whom fatty liver resolves over time is not known. Objective: The objective of the study was to assess the risk of incident diabetes at a 5-year follow-up in people in whom: 1) new fatty liver developed; 2) existing fatty liver resolved, and 3) fatty liver severity worsened over 5 years. Design and Methods: A total of 13 218 people without diabetes at baseline from a Korean occupational cohort were examined at baseline and after 5 years, using a retrospective study design. Fatty liver status was assessed at baseline and follow-up as absent, mild, or moderate/severe using standard ultrasound criteria. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for incident diabetes at follow-up were estimated after controlling for multiple potential confounders. Results: Two hundred thirty-four people developed incident diabetes. Over 5 years, fatty liver resolved in 828, developed in 1640, and progressed from mild to moderate/severe in 324 people. Resolution of fatty liver was not associated with a risk of incident diabetes [aOR 0.95 (95% CIs 0.46, 1.96), P = .89]. Development of new fatty liver was associated with incident diabetes [aOR 2.49 (95% CI 1.49, 4.14), P < .001]. In individuals in whom severity of fatty liver worsened over 5 years (from mild to moderate/severe), there was a marked increase in the risk of incident diabetes [aOR 6.13 (2.56, 95% CI 14.68) P < .001 (compared with the risk in people with resolution of fatty liver)]. Conclusion: Change in fatty liver status over time is associated with markedly variable risks of incident diabetes.

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Abstract P055: Changes in Red Meat Consumption and Subsequent Risk of Type 2 Diabetes: Three Cohorts of US Men and Women

Circulation ◽

10.1161/circ.127.suppl_12.ap055 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

An Pan ◽

Qi Sun ◽

JoAnn E Manson ◽

Walter C Willett ◽

Frank B Hu

Keyword(s):

Type 2 Diabetes ◽

Meat Consumption ◽

Red Meat ◽

Meat Intake ◽

Increased Risk ◽

Red Meat Intake ◽

Over Time ◽

Subsequent Risk

Introduction: Red meat consumption has been consistently associated with an increased risk of type 2 diabetes (T2D). However, it remains largely unknown whether changes in red meat intake are related to subsequent T2D risk. Methods: We followed 26,358 men in the Health Professionals Follow-up Study (HPFS, 1986-2006), 48,710 women in the Nurses’ Health Study (NHS, 1986-2006) and 74,077 women in NHS II (1991-2007). Diet was assessed by validated food frequency questionnaires and updated every 4 years. Incident T2D was confirmed by a validated supplementary questionnaire. Time-dependent Cox proportional hazard models were used to calculate relative risks (RRs) for changes in red meat consumption during a 4-year interval in relation to risk of T2D in the subsequent 4 years, with adjustment for age, family history, race, marital status, initial red meat consumption, initial and changes in other lifestyle factors (physical activity, smoking status, alcohol intake, and dietary quality). The results in the three cohorts were pooled by inverse-variance-weighted random-effects meta-analyses. Results: During 1,965,911 person-years of follow-up, we documented 7,521 incident T2D cases. In the multivariate-adjusted models, increasing red meat intake during a 4-year interval was associated with an increased risk of subsequent 4-year T2D risk in each cohort (all P-trend <0.001), and the pooled RR for one serving/d increment of red meat consumption was 1.30 (95% CI: 1.23, 1.38). The RR was attenuated to 1.20 (95% CI: 1.13, 1.27) after adjustment for baseline body mass index and concurrent weight change. We found significant interaction between initial red meat consumption and changes in red meat consumption with the subsequent risk of T2D; among participants with initial low (<2 servings/wk) or moderate (2-6 servings/wk) levels of red meat consumption, an increase of one serving/d during a 4-year interval was related to an elevated risk of incident T2D in the subsequent 4 years, and the pooled RR was 1.99 (95% CI: 1.47, 2.70) and 1.51 (95% CI: 1.25, 1.81), respectively. However, the association was much weaker (pooled RR 1.16; 95% CI: 1.05, 1.27) in individuals with high initial red meat consumption levels (≥1 serving/d), and the association was not linear in the HPFS and NHS II. Conclusions: Increasing red meat consumption over time is associated with an elevated subsequent risk of T2D, and the association is partly mediated by body weight changes. The association also depends on the initial red meat consumption levels. Our results add further evidence that limiting red meat consumption over time can confer benefits on diabetes prevention.

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Insulin use and new diabetes after acceptance for bariatric surgery: comparison of outcomes after completion of surgery or withdrawal from the program

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001837 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001837

Author(s):

Jessica H Lee ◽

Rebekah Jaung ◽

Grant Beban ◽

Nicholas Evennett ◽

Tim Cundy

Keyword(s):

Type 2 Diabetes ◽

Bariatric Surgery ◽

Glycated Hemoglobin ◽

Incident Diabetes ◽

High Relapse Rate ◽

Kaplan Meier ◽

Design And Methods ◽

Insulin Use

IntroductionIn people accepted onto a bariatric surgery program we compared diabetes-related outcomes in those who completed surgery with those who withdrew before having surgery—examining rates of insulin use in people with type 2 diabetes (T2D), and rates of incident diabetes in people without pre-existing T2D.Research design and methods771 people were accepted onto the program. 463 people (60%) had T2D at referral, of which 48% completed surgery and 52% withdrew. Of 308 people without T2D at referral, 49% completed surgery, and 51% withdrew. Rates of insulin use and incident diabetes were compared by Kaplan-Meier analyses. Among those with pre-existing T2D, we examined rates of remission and relapse after surgery.ResultsPeople without T2D who withdrew from the program had higher mean body mass index and glycated hemoglobin levels than those completing surgery (p<0.005). The rate of incident diabetes at 5 years was 19% in those who withdrew versus 0% in those completing surgery (p<0.001). 30% of people with T2D were taking insulin at referral and all stopped insulin after surgery. During follow-up, the rate of insulin (re)introduction was lower in those who completed surgery (8% vs 26% at 5 years, p<0.001). Of those with T2D who completed surgery, 80% had remission, but 34% had relapsed by 5 years. Diabetes relapse was associated with less weight loss after surgery, a longer duration of T2D and previous insulin use.ConclusionsDespite a high relapse rate, people with T2D who completed surgery had lower insulin use at 5 years than those withdrawing from the program. In people without T2D, bariatric surgery prevented incident diabetes. People without T2D who withdrew from the program were at greater risk of diabetes, suggesting those who could benefit the most in terms of T2D prevention are not completing bariatric surgery.

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Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001948 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001948

Author(s):

Marion Denos ◽

Xiao-Mei Mai ◽

Bjørn Olav Åsvold ◽

Elin Pettersen Sørgjerd ◽

Yue Chen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Family History ◽

Genetic Predisposition ◽

Effect Modification ◽

P Value ◽

Family History Of Diabetes ◽

Increased Risk ◽

History Of

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).ResultsOver 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).ConclusionSerum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

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TheType 2 Deiodinase Thr92Ala PolymorphismIs Associated with Worse Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Journal of Diabetes Research ◽

10.1155/2016/5928726 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 7

Author(s):

Xiaowen Zhang ◽

Jie Sun ◽

Wenqing Han ◽

Yaqiu Jiang ◽

Shiqiao Peng ◽

...

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glycemic Control ◽

Meta Analysis ◽

Increased Risk ◽

Design And Methods ◽

Hba1c Levels

Objective. Type 2 deiodinase (Dio2) is an enzyme responsible for the conversion of T4 to T3. The Thr92Ala polymorphism has been shown related to an increased risk for developing type 2 diabetes mellitus (T2DM). The aim of this study is to assess the association between this polymorphism and glycemic control in T2DM patients as marked by the HbA1C levels.Design and Methods.The terms “rs225014,” “thr92ala,” “T92A,” or “dio2 a/g” were used to search for eligible studies in the PubMed, Embase, and Cochrane databases and Google Scholar. A systematic review and meta-analysis of studies including both polymorphism testing and glycated hemoglobin (HbA1C) assays were performed.Results. Four studies were selected, totaling 2190 subjects. The pooled mean difference of the studies was 0.48% (95% CI, 0.18–0.77%), indicating that type 2 diabetics homozygous for the Dio2 Thr92Ala polymorphism had higher HbA1C levels.Conclusions. Homozygosity for the Dio2 Thr92Ala polymorphism is associated with higher HbA1C levels in T2DM patients. To confirm this conclusion, more studies of larger populations are needed.

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Changes in Glucose Tolerance over Time in Women with Polycystic Ovary Syndrome: A Controlled Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-1843 ◽

2005 ◽

Vol 90 (6) ◽

pp. 3236-3242 ◽

Cited By ~ 185

Author(s):

Richard S. Legro ◽

Carol L. Gnatuk ◽

Allen R. Kunselman ◽

Andrea Dunaif

Keyword(s):

Type 2 Diabetes ◽

Glucose Tolerance ◽

Polycystic Ovary ◽

Normal Glucose Tolerance ◽

Ovary Syndrome ◽

Normal Glucose ◽

Pcos Group ◽

Over Time

We performed this study to access the changes in glucose tolerance over time in a group of women with polycystic ovary syndrome (PCOS) (n = 71) and control women (n = 23) with regular menstrual cycles and baseline normal glucose tolerance. Mean follow-up was between 2 and 3 yr for both groups (PCOS 2.5 ± 1.7 yr; controls 2.9 ± 2.1 yr). Based on World Health Organization glucose tolerance categories, there was no significant difference in the prevalence of glucose intolerance at follow-up in the PCOS group. In the PCOS group, 25 (37%) had impaired glucose tolerance (IGT) and seven (10%) had type 2 diabetes mellitus at baseline, compared with 30 (45%) and 10 (15%), respectively, at follow-up. There were also no differences within groups (PCOS or control) or between groups (PCOS vs. control) in the oral glucose tolerance test-derived measure of insulin sensitivity, but in the women with PCOS who converted to either IGT or type 2 diabetes mellitus, there was a significant decrease (P < 0.0001). At the follow-up visit, the mean glycohemoglobin level was 6.1 ± 0.9% in women with PCOS vs. 5.3 ± 0.7% in the control women (P < 0.001). Women with PCOS and baseline IGT had a low conversion risk of 6% to type 2 diabetes over approximately 3 yr, or 2% per year. The effect of PCOS, given normal glucose tolerance (NGT) at baseline, is more pronounced with 16% conversion to IGT per year. Our study supports that women with PCOS (especially with NGT) should be periodically rescreened for diabetes due to worsening glucose intolerance over time, but this interval may be over several years and not annually.

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Elevated circulating follistatin associates with an increased risk of type 2 diabetes

Nature Communications ◽

10.1038/s41467-021-26536-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Chuanyan Wu ◽

Yan Borné ◽

Rui Gao ◽

Maykel López Rodriguez ◽

William C. Roell ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Genome Wide Association Study ◽

Regulatory Protein ◽

Alcoholic Fatty Liver ◽

Increased Risk

AbstractThe hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04–1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09–1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.

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Profibrotic circulating proteins and risk of early progressive renal decline in Type 2 Diabetes patients with and without albuminuria

10.2337/figshare.12808433.v1 ◽

2020 ◽

Author(s):

Katsuhito Ihara ◽

Jan Skupien ◽

Hiroki Kobayashi ◽

Zaipul I. Md Dom ◽

Jonathan M. Wilson ◽

...

Keyword(s):

Type 2 Diabetes ◽

Core Domain ◽

Fibrotic Process ◽

Baseline Levels ◽

Design And Methods ◽

Circulating Levels ◽

Index Combination

OBJECTIVE: The role of fibrosis in early progressive renal decline in type 2 diabetes is unknown. Circulating WFDC2 (WAP four-disulfide core domain protein 2) and MMP-7 (Matrilysin) are postulated to be biomarkers of renal fibrosis. This study examined an association of circulating levels of these proteins with early progressive renal decline. RESEARCH DESIGN AND METHODS: Individuals with type 2 diabetes enrolled in the Joslin Kidney Study with eGFR ≥60 ml/min/1.73m2 were followed for 6-12 years to ascertain fast early progressive renal decline defined as eGFR loss ≥5 ml/min/1.73m2/year. RESULTS: A total of 1,181 individuals were studied: 681 without and 500 with albuminuria. Median eGFR and ACR at baseline were 97 ml/min/1.73m2 and 24 mg/g, respectively. During follow-up, 152 individuals experienced fast early progressive renal decline: 6.9% in those with normoalbuminuria and 21% with albuminuria. In both subgroups risk of renal decline increased with increasing baseline levels of WFDC2 (p <0.0001) and MMP-7 (p <0.0001). After adjustment for relevant clinical characteristics and known biomarkers, an increase by one quartile in the Fibrosis Index (combination of levels of WFDC2 and MMP-7) was associated with higher risk of renal decline (OR 1.63; 95% CI 1.30-2.04). The association was similar and statistically significant among patients with and without albuminuria. CONCLUSIONS: Elevation of circulating profibrotic proteins is associated with the development of early progressive renal decline in type 2 diabetes. This association is independent from albuminuria status and points to the importance of the fibrotic process in development of early renal decline.

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Correlation between markers of renal function and sight-threatening diabetic retinopathy in type 2 diabetes: a longitudinal study in an Indian clinic population

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001325 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001325 ◽

Cited By ~ 1

Author(s):

Ramachandran Rajalakshmi ◽

Coimbatore Subramanian Shanthi Rani ◽

Ulagamathesan Venkatesan ◽

Ranjit Unnikrishnan ◽

Ranjit Mohan Anjana ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetic Retinopathy ◽

Serum Creatinine ◽

Cox Regression ◽

Tertiary Care ◽

Cox Regression Analysis ◽

Increased Risk ◽

New Onset

IntroductionPrevious epidemiological studies have reported on the prevalence of diabetic kidney disease (DKD) and diabetic retinopathy (DR) from India. The aim of this study is to evaluate the effect of DKD on the development of new-onset DR and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2D).Research design and methodsThe study was done on anonymized electronic medical record data of people with T2D who had undergone screening for DR and renal work-up as part of routine follow-up at a tertiary care diabetes center in Chennai, South India. The baseline data retrieved included clinical and biochemical parameters including renal profiles (serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria). Grading of DR was performed using the modified Early Treatment Diabetic Retinopathy Study grading system. STDR was defined as the presence of proliferative diabetic retinopathy (PDR) and/or diabetic macular edema. DKD was defined by the presence of albuminuria (≥30 µg/mg) and/or reduction in eGFR (<60 mL/min/1.73 m2). Cox regression analysis was used to evaluate the hazard ratio (HR) for DR and STDR.ResultsData of 19 909 individuals with T2D (mean age 59.6±10.2 years, mean duration of diabetes 11.1±12.1 years, 66.1% male) were analyzed. At baseline, DR was present in 7818 individuals (39.3%), of whom 2249 (11.3%) had STDR. During the mean follow-up period of 3.9±1.9 years, 2140 (17.7%) developed new-onset DR and 980 individuals with non-proliferative DR (NPDR) at baseline progressed to STDR. Higher serum creatinine (HR 1.5, 95% CI 1.3 to 1.7; p<0.0001), eGFR <30 mL/min/1.73 m2 (HR 4.9, 95% CI 2.9 to 8.2; p<0.0001) and presence of macroalbuminuria >300 µg/mg (HR 3.0, 95% CI 2.4 to 3.8; p<0.0001) at baseline were associated with increased risk of progression to STDR.ConclusionsDKD at baseline is a risk factor for progression to STDR. Physicians should promptly refer their patients with DKD to ophthalmologists for timely detection and management of STDR.

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Long-term BMI change trajectories in Chinese adults and its association with the hazard of type 2 diabetes: evidence from a 20-year China Health and Nutrition Survey

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000879 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000879

Author(s):

Baibing Mi ◽

Chenlu Wu ◽

Xiangyu Gao ◽

Wentao Wu ◽

Jiaoyang Du ◽

...

Keyword(s):

Type 2 Diabetes ◽

Latent Class ◽

Chinese Adults ◽

Change Trajectories ◽

Nutrition Survey ◽

Health And Nutrition ◽

Increased Risk

IntroductionTo investigate the relationship between long-term change trajectory in body mass index (BMI) and the hazard of type 2 diabetes among Chinese adults.Research design and methodsData were obtained from the China Health and Nutrition Survey (CHNS). Type 2 diabetes was reported by participants themselves in each survey wave. The duration of follow-up was defined as the period from the first visit to the first time self-reported type 2 diabetes, death, or other loss to follow-up from CHNS. The patterns of change trajectories in BMI were derived by latent class trajectory analysis method. The Fine and Gray regression model was used to estimate HRs with corresponding 95% CIs for type 2 diabetes.ResultsFour patterns of the trajectories of change in BMI were identified among Chinese adults, 42.7% of participants had stable BMI change, 40.8% for moderate BMI gain, 8.9% for substantial BMI gain and 7.7% for weight loss. During the follow-up with mean 11.2 years (158 637 person-years contributed by 14 185 participants), 498 people with type 2 diabetes (3.7%) occurred. Risk of type 2 diabetes was increased by 47% among people who gained BMI more substantially and rapidly (HR: 1.47, 95% CI 1.08 to 2.02, p=0.016) and increased by 20% among those in people with the moderate BMI gain (HR: 1.20, 95% CI 0.98 to 1.48, p=0.078), compared with those with stable BMI change.ConclusionsLong-term substantial gain of BMI was significantly associated with an increased risk of type 2 diabetes in the Chinese adults.

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Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts

Diabetologia ◽

10.1007/s00125-019-05001-w ◽

2019 ◽

Vol 62 (12) ◽

pp. 2298-2309 ◽

Cited By ~ 16

Author(s):

Ari V. Ahola-Olli ◽

Linda Mustelin ◽

Maria Kalimeri ◽

Johannes Kettunen ◽

Jari Jokelainen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Young Adults ◽

Fasting Glucose ◽

Diabetes Risk ◽

Increased Risk ◽

Metabolic Biomarkers ◽

Incident Cases ◽

Future Diabetes

Abstract Aims/hypothesis Metabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case−control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults. Methods NMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24–45 years). Associations between baseline metabolites and risk of developing diabetes during 8–15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up. Results Out of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59–1.50; p< 0.0009). Among the strongest biomarkers of diabetes risk were branched-chain and aromatic amino acids (OR 1.31–1.33) and triacylglycerol within VLDL particles (OR 1.33–1.50), as well as linoleic n-6 fatty acid (OR 0.75) and non-esterified cholesterol in large HDL particles (OR 0.59). The metabolic biomarkers were more strongly associated with deterioration in post-load glucose and insulin resistance than with future fasting hyperglycaemia. A multi-metabolite score comprised of phenylalanine, non-esterified cholesterol in large HDL and the ratio of cholesteryl ester to total lipid in large VLDL was associated with future diabetes risk (OR 10.1 comparing individuals in upper vs lower fifth of the multi-metabolite score) in one of the cohorts (mean age 31 years). Conclusions/interpretation Metabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk.

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