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Intramyocellular Triglyceride Content During the Early Course of Type 1 and Type 2 Diabetes.

ABSTRACT: Intramyocellular lipid content (IMCL) is elevated in insulin-resistant humans, but it changes over time, and relationships with comorbidities remain unclear. We examined IMCL during the initial course of diabetes and its associations with complications. Participants of the German Diabetes Study (GDS) with recent-onset type 1 (n = 132) or type 2 diabetes (n = 139) and glucose-tolerant control subjects (n = 128) underwent 1H-MRS to measure IMCL and muscle volume, whole-body insulin sensitivity (hyperinsulinemic-euglycemic clamps; M-value), and cycling spiroergometry (VO2max). Subgroups underwent the same measurements after 5 years. At baseline, IMCL was ∼30% higher in type 2 diabetes than in other groups independently of age, sex, BMI, and muscle volume. In type 2 diabetes, the M-value was ∼36% and ∼62% lower compared with type 1 diabetes and control subjects, respectively. After 5 years, the M-value decreased by ∼29% in type 1 and ∼13% in type 2 diabetes, whereas IMCL remained unchanged. The correlation between IMCL and M-value in type 2 diabetes at baseline was modulated by VO2max. IMCL also associated with microalbuminuria, the Framingham risk score for cardiovascular disease, and cardiac autonomic neuropathy. Changes in IMCL within 5 years after diagnosis do not mirror the progression of insulin resistance in type 2 diabetes but associate with early diabetes-related complications.

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Intramyocellular lipid content (IMCL) can be elevated in insulin-resistant humans, but its dynamics and association with comorbidities remain unclear. Independently of age, sex, body mass, and skeletal muscle volume, IMCL is higher in recent-onset type 2, but not type 1 diabetes, and remains unchanged within 5 years, despite worsening insulin resistance. A degree of physical fitness modulates the association between IMCL and insulin sensitivity in type 2 diabetes. Whereas higher IMCL associates with lower insulin sensitivity in people with lower physical fitness, there is no association between IMCL and insulin sensitivity in those with higher degree of physical fitness. IMCL associates with progression of microalbuminuria, cardiovascular disease risk, and cardiac autonomic neuropathy.

SUBMITTER: Schon M

PROVIDER: S-EPMC10545555 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Intramyocellular Triglyceride Content During the Early Course of Type 1 and Type 2 Diabetes.

Schön Martin M Zaharia Oana P OP Strassburger Klaus K Kupriyanova Yuliya Y Bódis Kálmán K Heilmann Geronimo G Strom Alexander A Bönhof Gidon J GJ Michelotti Filippo F Yurchenko Iryna I Möser Clara C Huttasch Maximilian M Bombrich Maria M Kelm Malte M Burkart Volker V Schrauwen-Hinderling Vera B VB Wagner Robert R Roden Michael M

Diabetes 20231001 10

Intramyocellular lipid content (IMCL) is elevated in insulin-resistant humans, but it changes over time, and relationships with comorbidities remain unclear. We examined IMCL during the initial course of diabetes and its associations with complications. Participants of the German Diabetes Study (GDS) with recent-onset type 1 (n = 132) or type 2 diabetes (n = 139) and glucose-tolerant control subjects (n = 128) underwent 1H-MRS to measure IMCL and muscle volume, whole-body insulin sensitivity (hy ...[more]

PMID: 37478166

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Project description:Background/objectivesAccumulation of lipid droplets inside skeletal muscle fibers (intramyocellular lipids or IMCL) with increasing obesity has been linked to skeletal muscle insulin resistance and risk of type 2 diabetes in both adults and prepubertal children. We aimed to evaluate the associations of race, genotype, prenatal factors, and postnatal factors with IMCL in early childhood.Subjects/methodsThis study was a secondary analysis performed on the GUSTO birth cohort. Soleus muscle IMCL of 392 children at 4.5 years of age was measured by magnetic resonance spectroscopy, of which usable imaging data were obtained from 277 children (137 Chinese, 87 Malays, and 53 Indians). Metabolic assessments (fasting glucose, insulin, and HOMA-IR) were performed at age 6.ResultsThe mean IMCL level at 4.5 years was 0.481 ± 0.279% of water resonance (mean ± sd). Corroborating with results from adults, Indian children had the highest IMCL levels compared with Malay and Chinese children. Among the prenatal factors, the rate of gestational weight gain (GWG rate) was associated with offspring IMCL (B = 0.396 (0.069, 0.724); p = 0.018). Both race and GWG rate continued to be associated with offspring IMCL even after accounting for current offspring BMI. Postnatally, IMCL was associated with shorter breastfeeding duration (B = 0.065 (0.001, 0.128); p = 0.045) and conditional relative weight gain between ages 2 and 3 (B = 0.052 (0.012, 0.093); p = 0.012). The associations with postnatal factors were attenuated after adjusting for current offspring BMI. IMCL was positively associated with offspring BMI (B = 0.028 (0.012, 0.044); p = 0.001). IMCL levels were not associated with fasting glucose, fasting insulin, and HOMA-IR at age 6.ConclusionThis study provides evidence that IMCL accumulation occurs in early childhood and that developmental factors and race are associated with it. We also show that early childhood IMCL accumulation is well tolerated, suggesting that the adverse associations between IMCL and insulin resistance may emerge at older ages.

Project description:PurposeTriglyceride-glucose (TyG) index is a reliable and inexpensive alternative indicator of insulin resistance. Previous studies have shown that elevated TyG index increases the risk of diabetes, coronary heart disease, and other diseases, but the relationship between TyG index and cardiac hemodynamics in patients with type 2 diabetes mellitus (T2DM) is not clear. This study was conducted in patients with T2DM to assess the relationship between TyG and cardiac hemodynamics and its predictive ability for T2DM.MethodsA total of 647 individuals (348 males and 299 females) were enrolled in this study, including 446 T2DM patients and 201 healthy controls. The clinical data and related laboratory variables were assessed and recorded, and TyG index was calculated. Cardiac hemodynamics was measured by echocardiography. Pearson or Spearman correlation analysis and linear regression analysis were conducted to explore the association between TyG and cardiac hemodynamics. The receiver operating characteristics (ROC) curve was used to evaluate the efficacy of TyG index in the diagnosis of T2DM.ResultsCompared with healthy controls, the systolic blood pressure (SBP), body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), HOMA-IR, and TyG levels were higher in patients with T2DM. With the increase of TyG, the levels of left ventricular mass index (LVMI), left ventricular mass (LVM), left ventricular end diastolic diameter (LVDd), posterior wall thickness (PWT), and interventricular septum thickness (IVST) were also increased in T2DM individuals. Multivariate linear regression analysis showed that TyG was an independent determinant of LVEF, PWT, IVST, and ejection time (ET) after adjusting for confounding factors. In addition, individuals with visceral obesity had higher TyG and TyG can be used as a predictor of T2DM with an AUC of 0.903 (95% CI:0.879-0.927).ConclusionsThe increase of TyG index is closely related to cardiac hemodynamics of T2DM patients, which is expected to be a simple and practical biological index to predict the changes of cardiac function in patients with T2DM.

Project description:ObjectiveWe aimed to evaluate the association of intrahepatic triglyceride (IHTG) content in subjects with metabolically healthy abdominal obesity (MHAO) on risks of pre-diabetes plus diabetes.DesignCross-sectional survey.SettingLianqian community, the First Affiliated Hospital of Xiamen University, Xiamen, China.ParticipantsAmong 1523 community-living healthy adults aged 40 years or older with abdominal obesity recruited at baseline, 428 subjects who underwent IHTG content measurement were selected.Outcome measuresRisk of pre-diabetes plus diabetes.ResultsNon-alcoholic fatty liver disease (NAFLD) was diagnosed as 203 (69.1%) in MHAO and 121 (90.3%) in metabolically unhealthy abdominal obesity (MUAO) (p<0.001). The prevalence rates of pre-diabetes plus diabetes were 81.1%, 88.8% and 90.9% across the tertiles of IHTG content (p=0.037). Both MUAO (vs MHAO) and NAFLD (vs non-NAFLD) were independently associated with increased risks of pre-diabetes plus diabetes, the adjusted ORs (95% CIs) were 10.90 (3.15 to 37.69, p<0.001) and 3.02 (1.47 to 6.20, p=0.003), respectively. Higher IHTG content was significantly associated with increased risk of pre-diabetes plus diabetes with the adjusted OR (95% CI) of per SD increase of IHTG content of 1.62 (1.07 to 2.46, p=0.024). And there was a significantly positive trend between increasing categories of IHTG content tertiles and excessive risks of pre-diabetes plus diabetes (trend test p value=0.011). Stratified analyses showed similar results on the associations of NAFLD and IHTG content with risks of pre-diabetes plus diabetes for subjects with MHAO but not for those with MUAO.ConclusionsNAFLD and higher IHTG content were independently associated with increased risks of pre-diabetes plus diabetes in MHAO subjects. NAFLD or quantity of liver fat should be considered as additional criterion when defining and diagnosing MHO. Screening of NAFLD and intervention to reduce liver fat should be strengthened even for those seemly metabolically healthy obese.

Project description:BackgroundReducing symptom burden is paramount at the end-of-life, but typically considered secondary to risk factor control in chronic disease, such as diabetes. Little is known about the symptom burden experienced by adults with type 2 diabetes and the need for symptom palliation.ObjectiveTo examine pain and non-pain symptoms of adults with type 2 diabetes over the disease course - at varying time points before death and by age.DesignSurvey follow-up study.Participants13,171 adults with type 2 diabetes, aged 30-75 years, from Kaiser Permanente, Northern California, who answered a baseline symptom survey in 2005-2006.Main measuresPain and non-pain symptoms were identified by self-report and medical record data. Survival status from baseline was categorized into ? 6, >6-24, or alive >24 months.Key resultsMean age was 60 years; 48 % were women, and 43 % were non-white. Acute pain was prevalent (41.8 %) and 39.7 % reported chronic pain, 24.6 % fatigue, 23.7 % neuropathy, 23.5 % depression, 24.2 % insomnia, and 15.6 % physical/emotional disability. Symptom burden was prevalent in all survival status categories, but was more prevalent among those with shorter survival, p<?.001. Adults ? 60 years who were alive >24 months reported more physical symptoms such as acute pain and dyspnea, whereas participants <60 years reported more psychosocial symptoms, such as depressed mood and insomnia. Adjustment for duration of diabetes and comorbidity reduced the association between age and pain, but did not otherwise change our results.ConclusionsIn a diverse cohort of adults with type 2 diabetes, pain and non-pain symptoms were common among all patients, not only among those near the end of life. However, symptoms were more prevalent among patients with shorter survival. Older adults reported more physical symptoms, whereas younger adults reported more psychosocial symptoms. Diabetes care management should include not only good cardiometabolic control, but also symptom palliation across the disease course.

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Intramyocellular Triglyceride Content During the Early Course of Type 1 and Type 2 Diabetes.

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Intramyocellular Triglyceride Content During the Early Course of Type 1 and Type 2 Diabetes.

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