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

Diabetes Care ◽

10.2337/dc21-1262 ◽

2021 ◽

Author(s):

Susan Martin ◽

Elena P. Sorokin ◽

E. Louise Thomas ◽

Naveed Sattar ◽

Madeleine Cule ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Mendelian Randomization ◽

Fat Content ◽

Liver Fat ◽

Liver And Pancreas ◽

Pancreas Volume

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 < 5 × 10−8) with the exposures (liver and pancreas volume and fat content) using MRI scans of UK Biobank participants (n = 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% increased risk and 0.76 [0.62, 0.94] or 24% 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.

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

10.2337/figshare.16959133.v1 ◽

2022 ◽

Author(s):

Susan Martin ◽

Elena P Sorokin ◽

E. Louise Thomas ◽

Naveed Sattar ◽

Madeleine Cule ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Mendelian Randomization ◽

Fat Content ◽

Liver Fat ◽

Liver And Pancreas ◽

Pancreas Volume

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 < 5×10−8) with the exposures (liver and pancreas volume and fat content) using MRI scans of UK Biobank participants (n=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 (OR) per one standard deviation (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 on risk of type 2 diabetes (1.27 [1.08,1.49] or 27% increased risk and 0.76 [0.62,0.94] or 24% 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.

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Reduced insulin clearance relates to increased liver fat content in recent-onset type 2 diabetes and to impaired glucose control in recent-onset type 1 diabetes

10.1055/s-0039-1688330 ◽

2019 ◽

Author(s):

S Antoniou ◽

OP Zaharia ◽

P Bobrov ◽

K Strassburger ◽

Y Karusheva ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Glucose Control ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

Recent Onset ◽

Onset Type

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Reduced insulin clearance relates to increased liver fat content in recent-onset type 2 diabetes and to impaired glucose control in recent-onset type 1 diabetes

Endocrine Abstracts ◽

10.1530/endoabs.67.o59 ◽

2019 ◽

Author(s):

Sofia Antoniou ◽

Oana P Zaharia ◽

Pavel Bobrov ◽

Klaus Strassburger ◽

Yanislava Karusheva ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Glucose Control ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

Recent Onset ◽

Onset Type

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The role of glycemic self-control in diabetes management: based on the American Diabetes Association guidelines (2021)

Medical Council ◽

10.21518/2079-701x-2021-12-286-292 ◽

2021 ◽

pp. 286-292

Author(s):

G. E. Runova

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

American Diabetes Association ◽

Diabetes Management ◽

Glucose Monitoring ◽

Self Monitoring ◽

Diabetes Technology

Glycemic control represents an integral part of diabetes mellitus (DM) therapy. It is not surprising that diabetes technology is evolving to not only create new routes of insulin administration, but also to improve the measurement of glycemia. A significant number of new glucose monitoring systems have been launched to the market over the past 10 years. Nevertheless, only 30% of patients with type 1 diabetes and very few patients with type 2 diabetes use continuous or flash glucose monitoring. The reason for this is not only the cost and technical difficulties of continuous glucose monitoring, but also its clinical appropriateness. There is indisputable evidence that patients who receive intensified insulin therapy, especially those with type 1 diabetes, need frequent self-monitoring / continuous glucose monitoring. As for patients with type 2 diabetes receiving basal insulin and / or other antihyperglycemic therapy, the data received seem to be contradictory and uncertain. However, most of the recommendations simmer down to the need for self-monitoring of blood glucose levels in patients with type 2 diabetes. The diabetes technology section of the American Diabetes Association guidelines 2021 goes into details about the role of self-monitoring of blood glucose in diabetes management, including the need for continuous patient education on the principles and rules of self-monitoring, interpretation and practical use of the results of self-monitoring, various standards of glucometers, factors affecting the accuracy of the results.

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NDUFB6 Polymorphism Is Associated With Physical Activity-Mediated Metabolic Changes in Type 2 Diabetes

Frontiers in Endocrinology ◽

10.3389/fendo.2021.693683 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dominik Pesta ◽

Tomas Jelenik ◽

Oana-Patricia Zaharia ◽

Pavel Bobrov ◽

Sven Görgens ◽

...

Keyword(s):

Physical Activity ◽

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Insulin Sensitivity ◽

Mitochondrial Function ◽

Liver Fat ◽

C2c12 Myotubes ◽

Clinical Trial Registration

The rs540467 SNP in the NDUFB6 gene, encoding a mitochondrial complex I subunit, has been shown to modulate adaptations to exercise training. Interaction effects with diabetes mellitus remain unclear. We assessed associations of habitual physical activity (PA) levels with metabolic variables and examined a possible modifying effect of the rs540467 SNP. Volunteers with type 2 (n=242), type 1 diabetes (n=250) or normal glucose tolerance (control; n=139) were studied at diagnosis and subgroups with type 1 (n=96) and type 2 diabetes (n=95) after 5 years. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps, oxygen uptake at the ventilator threshold (VO2AT) by spiroergometry and PA by questionnaires. Translational studies investigated insulin signaling and mitochondrial function in Ndufb6 siRNA-treated C2C12 myotubes, with electronic pulse stimulation (EPS) to simulate exercising. PA levels were 10 and 6%, VO2AT was 31% and 8% lower in type 2 and type 1 diabetes compared to control. Within 5 years, 36% of people with type 2 diabetes did not improve their insulin sensitivity despite increasing PA levels. The NDUFB6 rs540467 SNP modifies PA-mediated changes in insulin sensitivity, body composition and liver fat estimates in type 2 diabetes. Silencing Ndufb6 in myotubes reduced mitochondrial respiration and prevented rescue from palmitate-induced insulin resistance after EPS. A substantial proportion of humans with type 2 diabetes fails to respond to rising PA with increasing insulin sensitivity. This may at least partly relate to a polymorphism of the NDUFB6 gene, which may contribute to modulating mitochondrial function.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01055093. The trial was retrospectively registered on 25th of January 2010.

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1888-P: Impaired Insulin Clearance Relates to Increased Liver Fat Content in Recent-Onset Type 2 Diabetes and to Impaired Glucose Control in Recent-Onset Type 1 Diabetes

Diabetes ◽

10.2337/db19-1888-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 1888-P

Author(s):

SOFIA ANTONIOU ◽

OANA P. ZAHARIA ◽

KLAUS STRASSBURGER ◽

YANISLAVA KARUSHEVA ◽

KALMAN BODIS ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Glucose Control ◽

Liver Fat ◽

Liver Fat Content ◽

Recent Onset ◽

Onset Type ◽

Impaired Insulin

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6. Appetite, fat, and obesity

Hormones: A Very Short Introduction ◽

10.1093/actrade/9780199672875.003.0006 ◽

2014 ◽

pp. 74-87

Author(s):

Martin Luck

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 1 Diabetes ◽

The Body ◽

Storage Process ◽

Lifestyle Disease ◽

Energy Shortage

‘Appetite, fat, and obesity’ considers the role of insulin in the body’s fat storage process. In the condition diabetes mellitus, the sugar level in the blood rises uncontrollably so the kidneys cannot stop it leaking into the urine. Type 1 diabetes is an autoimmune disease in which a person’s immune system attacks the insulin-secreting β-cells of the pancreas. The only effective treatment is to inject the missing insulin. Type 2 diabetes is considered more of a lifestyle disease. But what exactly is the connection between obesity and poorly regulated blood glucose? The body has more hormones capable of responding to energy shortage than to energy abundance, which may be why keeping control of body weight can be difficult. The hormones affecting appetite are also discussed.

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