Fat Distribution Patterns and Future Type 2 Diabetes

Abstract

Fat accumulation in the liver, pancreas, skeletal muscle, and visceral bed relates to type-2 diabetes (T2D). However, the distribution of fat among these compartments is heterogenous and it is unclear whether specific distribution patterns indicate high T2D risk. We therefore investigated fat-distribution patterns and their link to future T2D. From 2168 individuals without diabetes who underwent computed tomography in Japan, this case-cohort study included 658 randomly selected individuals and 146 incident cases of T2D over 6 years of follow-up. Using data-driven analysis (k-means) based on fat content in the liver, pancreas, muscle, and visceral bed, we identified four fat-distribution clusters: Hepatic steatosis, Pancreatic steatosis, Trunk myosteatosis, and Steatopenia. Compared with the Steatopenia cluster, the adjusted hazard ratios (95% CIs) for incident T2D were 4.02 (2.27-7.12) for the Hepatic steatosis cluster, 3.38 (1.65-6.91) for the Pancreatic steatosis cluster, and 1.95 (1.07-3.54) for the Trunk myosteatosis cluster. The clusters were replicated in 319 German individuals without diabetes who underwent magnetic resonance imaging and metabolic phenotyping. The distribution of AUC-glucose across the four clusters found in Germany was similar to the distribution of T2D risk across the four clusters in Japan. Insulin sensitivity and insulin secretion differed across the four clusters. Thus, we identified patterns of fat distribution with different T2D risks presumably due to differences in insulin sensitivity and insulin secretion.

Hepatic follistatin increases basal metabolic rate and attenuates diet-induced obesity during hepatic insulin resistance

“…Lower body fat content is generally considered metabolically beneficial; however, the storage of triglyceride safely in WAT is also an important aspect of metabolic health [ 70 ]. Our previous work shows that uncontrolled adipose lipolysis stimulated by high circulating hepatic Fst in LDKO mice potentiates hepatic gluconeogenesis and diabetes [ 18 ].…”

Metabolic traits affecting the relationship between liver fat and intrapancreatic fat: a mediation analysis

“…The predictions of this hypothesis were subsequently confirmed in interventional studies of a low-energy diet: the Counterpoint, Counterbalance and DiRECT trials [ 37 – 39 ]. Further, a 2022 data-driven cluster analysis partitioned individuals without diabetes based on their abdominal fat distribution and then studied the longitudinal association of membership in the resulting clusters with incident type 2 diabetes [ 40 ]. The study showed that individuals with excess liver fat and those with excess IPFD (but not those with excess skeletal muscle fat deposition) are at remarkably similar (fourfold and 3.4-fold higher, respectively) risk of type 2 diabetes, further supporting the link between liver fat and IPFD [ 40 ].…”

“…Further, a 2022 data-driven cluster analysis partitioned individuals without diabetes based on their abdominal fat distribution and then studied the longitudinal association of membership in the resulting clusters with incident type 2 diabetes [ 40 ]. The study showed that individuals with excess liver fat and those with excess IPFD (but not those with excess skeletal muscle fat deposition) are at remarkably similar (fourfold and 3.4-fold higher, respectively) risk of type 2 diabetes, further supporting the link between liver fat and IPFD [ 40 ]. The use of the path-analytic methodological framework and the large sample size of the present observational study enabled us to provide robust complementary evidence that supports the interconnectedness of IPFD and liver fat.…”

Relationships of adiponectin to regional adiposity, insulin sensitivity, serum lipids, and inflammatory markers in sedentary and endurance-trained Japanese young women

“…The lower-body region is one of the major areas for the accumulation of subcutaneous adipose tissue. Different adipose depositions have been recognized to cause different metabolic consequences ( 9 , 10 ). Those who accumulate fat tissue in the trunk region (android obese) are more likely to develop diabetes and cardiovascular diseases (CVDs) than those with major lower-body-fat mass (LFM) deposition (gynoid obese) ( 10 ).…”

“…Different adipose depositions have been recognized to cause different metabolic consequences ( 9 , 10 ). Those who accumulate fat tissue in the trunk region (android obese) are more likely to develop diabetes and cardiovascular diseases (CVDs) than those with major lower-body-fat mass (LFM) deposition (gynoid obese) ( 10 ). One of the reasons for the higher prevalence of CVDs in men than in women is that men tend to develop android obesity, whereas women tend to develop gynoid obesity ( 11 ).…”