New Type 2 Diabetes Risk Factors Identified

Martin, S. et al | 2021| Estimating the Effect of Liver and Pancreas Volume and Fat Content on Risk of Diabetes: A Mendelian Randomization Study | Diabetes Care | dc211262. https://doi.org/10.2337/dc21-1262

Type 2 diabetes (T2D) is associated with a number of risk factors and now new research, published in Diabetes Care, suggests that increased levels of liver fat and a smaller pancreas volume may also add to a greater risk of developing T2D.

The new study, conducted at Brunel University, used data collected from 32,859 people who underwent an MRI as part of the UK Biobank study. Data from 9358 participants with type 1 diabetes was also collected from various genome-wide association studies.

“People with type 2 diabetes usually have excess fat in their liver and pancreas, the two key organs in the maintenance of the normal level of blood sugar. The genetic analysis we used in this study is the best possible method to test this relationship,” says Dr Yaghootkar. (via MedScape).

OBJECTIVE

Fat content and volume of liver and pancreas are associated with risk of diabetes in observational studies; whether these associations are causal is unknown. We conducted a Mendelian randomization (MR) study to examine causality of such associations.

RESEARCH DESIGN AND METHODS

We used genetic variants associated (P less than 5 × 10−8) with the exposures (liver and pancreas volume and fat content) using MRI scans of UK Biobank participants (n equal to 32 859). We obtained summary-level data for risk of type 1 (9 358 cases) and type 2 (55 005 cases) diabetes from the largest available genome-wide association studies. We performed inverse–variance weighted MR as main analysis and several sensitivity analyses to assess pleiotropy and to exclude variants with potential pleiotropic effects.

RESULTS

Observationally, liver fat and volume were associated with type 2 diabetes (odds ratio per 1 SD higher exposure 2.16 [2.02, 2.31] and 2.11 [1.96, 2.27], respectively). Pancreatic fat was associated with type 2 diabetes (1.42 [1.34, 1.51]) but not type 1 diabetes, and pancreas volume was negatively associated with type 1 diabetes (0.42 [0.36, 0.48]) and type 2 diabetes (0.73 [0.68, 0.78]). MR analysis provided evidence only for a causal role of liver fat and pancreas volume in risk of type 2 diabetes (1.27 [1.08, 1.49] or 27 per cent increased risk and 0.76 [0.62, 0.94] or 24 per cent decreased risk per 1SD, respectively) and no causal associations with type 1 diabetes.

CONCLUSIONS

Our findings assist in understanding the causal role of ectopic fat in the liver and pancreas and of organ volume in the pathophysiology of type 1 and 2 diabetes.

MedScape New Type 2 Diabetes Risk Factors Identified

Estimating the Effect of Liver and Pancreas Volume and Fat Content on Risk of Diabetes: A Mendelian Randomization Study [paper]

Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies

Yuan, J. et al. (2020). Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies | BMJ Gut| https://gut.bmj.com/content/early/2020/08/29/gutjnl-2020-322557

New evidence indicates that taking acid reflux drugs on a regular basis may increase an individual’s risk of developing type 2 diabetes. BMJ Gut has published research that analysed data from over 200 000 participants who did not have diabetes at the study’s outset, researchers observed the risk of developing diabetes following regular ingestion of proton pump inhibitors (PPSIs) rose by a quarter, an even more marked risk was noted in individuals who used the reflux drugs over longer periods of time.

Significance of this study
What is already known about this subject?
  • Despite the irreplaceable role of proton pump inhibitors (PPIs) in clinical practice, long-term use of PPIs has been linked to a series of health problems such as bone fracture and enteric infections.
  • PPIs have a major impact on gut microbiome which, in turn, may increase the risk of type 2 diabetes, but epidemiological evidence remains unclear.
What are the new findings?
  • In this prospective analysis of 204 689 participants free of diabetes from three ongoing US cohorts, regular use of PPIs was associated with a 24% increased risk of diabetes even after adjusting for putative risk factors and indications for use, with a higher risk observed in individuals with a longer duration of PPI use.
How might it impact on clinical practice in the foreseeable future?
  • Physicians should be aware of the potential risk of type 2 diabetes when prescribing PPIs, particularly for long-term treatment.
  • Screening for abnormal blood glucose and type 2 diabetes may be required for regular PPI users, particularly for high-risk populations.

Abstract

Objective The association between the regular use of proton pump inhibitors (PPIs) and the risk of type 2 diabetes remains unclear, although a recent randomised controlled trial showed a trend towards increased risk. This study was undertaken to evaluate the regular use of PPIs and risk of type 2 diabetes.

Method This is a prospective analysis of 204 689 participants free of diabetes in the Nurses’ Health Study (NHS), NHS II and Health Professionals Follow-up Study (HPFS). Type 2 diabetes was confirmed using American Diabetes Association (ADA) diagnostic criteria. We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, the presence of comorbidities, use of other medications and clinical indications.

Results We documented 10 105 incident cases of diabetes over 2 127 471 person-years of follow-up. Regular PPI users had a 24% higher risk of diabetes than non-users. The risk of diabetes increased with duration of PPI use. Fully adjusted HRs were 1.05 for participants who used PPIs for >0–2 years and 1.26 for participants who used PPIs for >2 years compared with non-users.

Conclusions Regular use of PPIs was associated with a higher risk of type 2 diabetes and the risk increased with longer duration of use. Physicians should therefore exercise caution when prescribing PPIs, particularly for long-term use.

Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies

Type 2 diabetes in midlife and risk of cerebrovascular disease in late life: a prospective nested case−control study in a nationwide Swedish twin cohort

 Yang, R. et al | 2019| Type 2 diabetes in midlife and risk of cerebrovascular disease in late life: a prospective nested case−control study in a nationwide Swedish
twin cohort| Diabetologia |https://doi.org/10.1007/s00125-019-4892-3

Research from Sweden studied the association between diabetes mellitus type 2 in midlife (40-59 years) and cerebrovascular disease in late life. The study explored the incidence of CBD in over 300,000 twins who were CBD-free at the outset of the study. 

Midlife type 2 diabetes is significantly associated with increased risk of cerebral infarction and occlusion of cerebral arteries, but not intracerebral haemorrhage or subarachnoid haemorrhage in late life. The researchers report that genetic and early-life familial environmental factors do not appear to account for the type 2 diabetes.

canvas-1009232_640.jpg

The findings of this study are now published in Diabetologia 

In the news:

OnMedica Possible link between diabetes and cerebrovascular disease

 

Abstract

Aims/hypothesis

We aimed to examine the association between midlife type 2 diabetes mellitus and cerebrovascular disease (CBD) in late life, and further to explore whether genetic and early-life familial environmental factors (such as shared childhood socioeconomic status and adolescent environment) play a role in this association.

Methods

In this prospective nested case−control study based on the Swedish Twin Registry, 33,086 twin individuals who were born in 1958 or earlier and were CBD-free before the age of 60 were included. Midlife (40–59 years) type 2 diabetes was ascertained from self-report, the National Patient Registry (NPR) and glucose-lowering medication use. CBD diagnosis (cerebral infarction, occlusion of cerebral arteries, subarachnoid haemorrhage, intracerebral haemorrhage and unspecified CBD) and onset age were identified from the NPR. Late-life CBD was defined as CBD onset aged 60 years or over. Generalised estimating equation (GEE) models were used to analyse unmatched case−control data (adjusted for the clustering of twins within a pair). Conditional logistic regression was used in co-twin matched case−control analyses in CBD-discordant twin pairs.

Results

Of all the participants, 1248 (3.8%) had midlife type 2 diabetes and 3121 (9.4%) had CBD in late life. In GEE models adjusted for age, sex, education, BMI, smoking, alcohol consumption, marital status, hypertension and heart disease, the ORs of type 2 diabetes were 1.29 for cerebral infarction, 2.03 for occlusion of cerebral arteries, 0.52  for subarachnoid haemorrhage and 0.78  for intracerebral haemorrhage. In multi-adjusted conditional logistic regression, the OR of the type 2 diabetes–cerebral infarction association was 0.96. The differences in ORs from the GEE and co-twin control analyses were not statistically significant.

Conclusions/interpretation

Midlife type 2 diabetes is significantly associated with increased risk of cerebral infarction and occlusion of cerebral arteries, but not intracerebral haemorrhage or subarachnoid haemorrhage in late life. Genetic and early-life familial environmental factors do not appear to account for the type 2 diabetes–cerebral infarction association, but further clarification is needed.

The full article is available from Diabetologia 

Type 2 diabetes in midlife and risk of cerebrovascular disease in late life: a prospective nested case−control study in a nationwide Swedish twin cohort

Shift work increases diabetes and heart disease risk

Many studies have shown that shift work is associated with heart and metabolic diseases, but new research has clarified how shift work can have a long-term effect on the risk of heart disease and diabetes | Experimental Physiology | via ScienceDaily

work-3992714_1280

With over 20% of the population in industrial countries engaging shift work — in sectors such as healthcare and transportation — we urgently need to understand its health burden.

Many studies have shown that shift work is associated with heart and metabolic diseases, but new research in Experimental Physiology has clarified how shift work can have a long-term effect on the risk of heart disease and diabetes.

The study specifically suggested that shift work has a negative impact on the way a type of fat (called triglycerides) is broken down, as well as on the way sugar is utilised in our bodies. Both of these increase the risk of heart disease and diabetes because they affect how our body processes sugar and fat.

Full story: The Physiological Society | Shift work increases diabetes and heart disease risk |  ScienceDaily | 2 April 2019.

Full article: Keithellakpam Kiranmala, et al. |  Association of postprandial triglyceride responses with insulin resistance among rotational night shift healthcare workers | Experimental Physiology | 2019 |  DOI: 10.1113/EP087514

 

Obesity and diabetes both linked to cancer

Diabetes and high BMI are leading causes of death and ill health globally and are on the increase in most countries. In 2014 9% of men and 8% of women worldwide had diabetes; 38.5% of men and 39.2% of women had high Body Mass Index (BMI), a figure equivalent to approximately 2 billion adults. 

A high BMI was responsible for almost twice as many cancers as diabetes. Over 5% of cancers worldwide were attributable to diabetes or high BMI in 2012, it is estimated that this proportion may increase by 25% by 2035 as a result of the global increase in obesity. 

obese-3011213_1920

For countries such as the UK, an estimated 15% to 16% of cancers could be avoided by preventing diabetes, obesity or excess weight (defined as a BMI  greater than 25). A high BMI was responsible for almost twice as many cancers as diabetes.

Although the links between high BMI, diabetes and cancer have been known for some time, this study presents the first calculations of attributable risk for 175 countries. This represents the proportion of cancers that could be prevented if the risk factors were eliminated.  (The National Institute of Health Research NIHR)

The abstract is taken from NIHR

Abstract
Background
Diabetes and high body-mass index (BMI) are associated with increased risk of several cancers, and are increasing in prevalence in most countries. We estimated the cancer incidence attributable to diabetes and high BMI as individual risk factors and in combination, by country and sex.Methods We estimated population attributable fractions for 12 cancers by age and sex for 175 countries in 2012. We defined high BMI as a BMI greater than or equal to 25 kg/m2. We used comprehensive prevalence estimates of diabetes and BMI categories in 2002, assuming a 10-year lag between exposure to diabetes or high BMI and incidence of cancer, combined with relative risks from published estimates, to quantify contribution of diabetes and high BMI to site-specific cancers, individually and combined as independent risk factors and in a conservative scenario in which we assumed full overlap of risk of diabetes and high BMI. We then used GLOBOCAN cancer incidence data to estimate the number of cancer cases attributable to the two risk factors. We also estimated the number of cancer cases in 2012 that were attributable to increases in the prevalence of diabetes and high BMI from 1980 to 2002. All analyses were done at individual country level and grouped by region for reporting.

Findings We estimated that 5·6% of all incident cancers in 2012 were attributable to the combined effects of diabetes and high BMI as independent risk factors, corresponding to 792 600 new cases. 187 600 (24·5%) of 766 000 cases of liver cancer and 121 700 (38·4%) of 317 000 cases of endometrial cancer were attributable to these risk factors. In the conservative scenario, about 4·5% (626 900 new cases) of all incident cancers assessed were attributable to diabetes and high BMI combined. Individually, high BMI (544 300 cases) was responsible for twice as many cancer cases as diabetes (280 100 cases). 26·1% of diabetes-related cancers (equating to 77 000 new cases) and 31·9% of high BMI-related cancers (174 040 new cases) were attributable to increases in the prevalence of these risk factors from 1980 to 2002.

Interpretation A substantial number of cancer cases are attributable to diabetes and high BMI. As the prevalence of these cancer risk factors increases, clinical and public health efforts should focus on identifying optimal preventive and screening measures for whole populations and individual patients.

Full reference:  Pearson-Stuttard, J. et al |Worldwide burden of cancer attributable to diabetes and high body mass index: a comparative risk assessment|The Lancet Diabetes & Endocrinology|2017

The article can downloaded from The Lancet here 

Physical exercise may lower risk of developing diabetes in high risk individuals

University of Birmingham scientists in conjunction with Chinese researchers, studied  the incidence of  type 2 diabetes in a prospective cohort study of Chinese adults with impaired fasting glucose (IFG).44 828. The adults age range was between 20-80 years with newly detected IFG but free from cardiovascular and cerebrovascular disease were recruited and followed their health from 1996 to 2014.

The researchers  found an association between individuals who engage in physical activity and lower risk of diabetes, in people who have a high risk of developing the condition.  Studying an IFG population in Taiwan, compared with inactive participants, diabetes risk in individuals reporting low, moderate and high volume  leisure-time physical activity (LTPA) was reduced by 12%, 20%, and 25% respectively after adjusting for physical labour at work and other factors.

The researchers found that 19.2% of diabetes cases could have been avoided if the inactive participants had engaged in WHO recommendation levels of LTPA.

Full story from Science Daily 
park-life-2251981_1920

Abstract

Aims To evaluate the effects of habitual leisure-time physical activity (LTPA) on incident type 2 diabetes in a prospective cohort of Chinese adults with impaired fasting glucose (IFG).

Methods 44 828 Chinese adults aged 20–80 years with newly detected IFG but free from cardiovascular and cerebrovascular disease were recruited and followed up from 1996 to 2014. Incident type 2 diabetes was identified by fasting plasma glucose ≥7 mmol/L. The participants were classified into four categories based on their self-reported weekly LTPA: inactive, low, moderate, or high. Hazard ratios (HRs) and population attributable fractions (PAFs) were estimated with adjustment for established diabetic risk factor.

Results After 214 148 person-years of follow-up, we observed an inverse dose–response relationship between LTPA and diabetes risk. Compared with inactive participants, diabetes risk in individuals reporting low, moderate and high volume LTPA were reduced by 12% (HR 0.88, 95% CI 0.80 to 0.99; P=0.015), 20% (HR 0.80, 95% CI 0.71 to 0.90; P less than 0.001), and 25% (HR 0.75, 95% CI 0.67 to 0.83; P less than 0.001), respectively. At least 19.2% (PAF 19.2%, 95% CI 5.9% to 30.6%) of incident diabetes cases could be avoided if the inactive participants had engaged in WHO recommendation levels of LTPA. This would correspond to a potential reduction of at least 7 million diabetic patients in the Greater China area.

Conclusions Our results show higher levels of LTPA are associated with a lower risk of diabetes in IFG subjects. These data emphasise the urgent need for promoting physical activity as a preventive strategy against diabetes to offset the impact of population ageing and the growing obesity epidemic.

Full reference: Xiang, Q.L. et al | Increased leisure-time physical activity associated with lower onset of diabetes in 44 828 adults with impaired fasting glucose: a population-based prospective cohort study | British Journal of Sports Medicine| 2018 |DOI: 10.1136/bjsports-2017-098199

The full text article can be requested by Rotherham NHS staff here 

Night Shift Work and Type 2 Diabetes in the UK

New study looking at the connection between shift work and type 2 diabetes finds that more frequent night work increased the odds of type 2 diabetes, regardless of genetic type 2 diabetes risk. | Diabetes Care | via ScienceDaily

moon-1527501_1920 (1)

A team of researchers examined data on hundreds of thousands of people in the UK Biobank to better understand how shift work — especially frequent night work — contributes to the likelihood of type 2 diabetes. The team also developed a genetic risk score for type 2 diabetes, examining genetic data for tens of thousands of workers in the database. They found that more frequent night work increased the odds of type 2 diabetes, regardless of genetic type 2 diabetes risk, among the population studied.

Those with the highest genetic risk scores were almost four times as likely to develop type 2 diabetes compared to individuals who had lower genetic risk scores. Those who reported working irregular or rotating shifts with usual night shifts were 44 percent more likely to have type 2 diabetes, after taking into account other established risk factors.

Full story at ScienceDaily

Full reference: Vetter, C et al. | Night Shift Work, Genetic Risk, and Type 2 Diabetes in the UK Biobank | Diabetes Care |  February 2018

Cataract in patients with diabetes mellitus—incidence rates in the UK and risk factors

According to researchers from Anglia Ruskin University diabetes doubles the risk of developing cataract compared to the rest of the population. Diabetics in the study aged between 45 and 54 were considerably more likely than non-sufferers to develop cataract.

eye-321961_1280

Although this study is only the second report on cataract incidence in the UK’s diabetic patients since the 1980s, Rupert Bourne Professor of Opthalmology at Anglia Ruksin explains this “emphasises the importance of the NHS Diabetic Eye Screening programme in early identification and treatment of diabetic eye disease to prevent sight loss.”

Aims
To analyze the risk of incident cataract (diagnosis or extraction) in patients with or without diabetes focusing on other comorbid conditions, antidiabetic drug use, and diabetes duration.

Methods
The study population comprised newly diagnosed diabetes patients (≥40 years) from the UK-based Clinical Practice Research Datalink (CPRD) between 2000 and 2015, and a random sample of the general population matched for age, sex, general practice, and year of diabetes diagnosis.

Results
There were 56,510 diabetes patients included in the study. IRs increased considerably around the age of 80 years and with a concomitant diagnosis of macular edema. The incidence rate ratio (IRR) was highest in patients of the age group of 45–54 years. In the nested case-control study, we identified 5800 patients with cataract. Risk of cataract increased with increasing diabetes duration (adj. OR 5.14, 95% CI 4.19–6.30 diabetes for ≥10 years vs. diabetes <2 years).

Conclusions
According to our study, diabetes is associated with an approximately two-fold increased detection rate of cataract. The risk of cataract associated with diabetes is highest at younger ages. Patients with diabetic macular edema are at an increased risk for cataract as well as patients with long-standing diabetes.

The full abstract is available from the journal  Eye

Full reference:  Becker, C. et al. | Cataract in patients with diabetes mellitus- incidence rates in the UK and risk factors | Eye | Vol. 1 | 2018 | doi: 10.1038/s41433-017-0003-1

This article can be requested by Rotherham NHS staff

People with diabetes face increased risk of infections

Diabetes patients have an increased risk of suffering serious infections or death compared to the general public, new research has shown | Diabetes Care | Story via ScienceDaily

A study carried out by the University of Glasgow analysed the electronic GP and hospital records of more than 100,000 English adults aged 40 to 89 years with a diabetes diagnosis, and compared them to those without a diabetes diagnosis.

The researchers estimated that 6% of infection-related hospital admissions, such as for pneumonia, and 12% of infection-related deaths among adults could be attributed to diabetes.

The large size of the study enabled the researchers to show that diabetes patients with the less common Type 1 diagnosis were at even greater risk of being hospitalised and dying from infection.

Over a seven year period, patients with Type 2 diabetes were twice as likely to be hospitalised with an infection as patients without diabetes; for Type 1 diabetes this difference was nearly four times.

The study also investigated more common infections seen by GPs, and found that skin infections such as cellulitis were twice as common in patients with diabetes.

Full story at ScienceDaily

Full reference: Carey, I.M. et al. | Risk of Infection in Type 1 and Type 2 Diabetes Compared With the General Population: A Matched Cohort Study | Diabetes Care, 2018