Association between KLF6 rs3750861 polymorphism and plasma ceramide concentrations in post-menopausal women with type 2 diabetes

Background and aimBased on the emerging role of Kruppel-like factor 6 (KLF6) in lipid metabolism, we examined whether there is a relationship between the KLF6 rs3750861 genetic variant and plasma ceramide levels in people with type 2 diabetes mellitus (T2DM).Methods and resultWe measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] amongst 101 Caucasian post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramides were measured by targeted liquid chromatography-tandem mass spectrometry assay. Genotyping of the KLF6 rs3750861 polymorphism was performed by TaqMan-Based RT-PCR system.Overall, 87 (86.1%) patients had KLF6 rs3750861 C/C genotype and 14 (13.9%) had C/T or T/T genotypes. After adjustment for age, diabetes-related variables, use of lipid-lowering drugs and other potential confounders, patients with C/T or T/T genotypes had higher plasma Cer(d18:1/18:0) (0.159 ± 0.05 vs. 0.120 ± 0.04 μmol/L, p = 0.012), Cer(d18:1/20:0) (0.129 ± 0.04 vs. 0.098 ± 0.03 μmol/L, p = 0.008), and Cer(d18:1/24:1) (1.236 ± 0.38 vs. 0.978 ± 0.36 μmol/L, p = 0.032) compared with those with C/C genotype.ConclusionsThe C/T or T/T genotypes of rs3750861 in the KLF6 gene were closely associated with higher levels of specific plasma ceramides in post-menopausal women with T2DM.     

Correlation between basal metabolic rate,visceral fat and insulin resistance among type 2 diabetes mellitus with peripheral neuropathy

BackgroundBasal Metabolic Rate (BMR) means the amount of energy utilized by body in physical and psychological resting rate, after a night sleep, awake without any previous physical activity post meal (10 h after last meal) & neutral environment. In people with type 2 diabetes mellitus (T2DM) there is an increase in BMR which is said to be associated with the level of glycaemic control. So, the objective of the study was to find out the correlation between BMR, Insulin resistance and Visceral fat in T2DM with peripheral neuropathy.Materials & methodsA total of 50 participants with T2DM with peripheral neuropathy were included. Age group of 30–75 years were selected for the study. Participants with a known history of neurological disease, locomotor disability, and pregnancy were excluded from the study. Demographic details of the participants like duration of diabetes mellitus, age, Fasting Blood Glucose, Fasting Insulin, HOMA-IR, Glycated Haemoglobin (HBA1c), Neuropathy and Blood pressure values were noted. We measured Basal Metabolic Rate (BMR) by using Mifflin-St Jeor predictive equation in T2DM with peripheral neuropathy.ResultsThe mean age of the participants is 60.16 ± 10.62. The mean duration of T2DM 13.44 ± 11.92. In the present study we found a statistical significant correlation between BMR and HOMA IR (r = 0.913*; p = 0.000), BMR & Fasting blood sugar (FBS) (r = 0.281*; p = 0.048), BMR and Visceral fat (VF) (r = 0.332*; p = 0.018).ConclusionBasal metabolic rate is correlated to Homa-IR, visceral fat, fasting blood sugar and musculoskeletal mass among T2DM with peripheral neuropathy.     

Role of myokines in the development of skeletal muscle insulin resistance and related metabolic defects in type 2 diabetes

Due to its mass, skeletal muscle is the major site of glucose uptake and an important tissue in the development of type 2 diabetes (T2D). Muscles of patients with T2D are affected with insulin resistance and mitochondrial dysfunction, which result in impaired glucose and fatty acid metabolism. A well-established method of managing the muscle metabolic defects occurring in T2D is physical exercise. During exercise, muscles contract and secrete factors called myokines which can act in an autocrine/paracrine fashion to improve muscle energy metabolism. In patients with T2D, plasma levels as well as muscle levels (mRNA and protein) of some myokines are upregulated, while others are downregulated. The signalling pathways of certain myokines are also altered in skeletal muscle of patients with T2D. Taken together, these findings suggest that myokine secretion is an important factor contributing to the development of muscle metabolic defects during T2D. It is also of interest considering that lack of physical activity is closely linked to the occurrence of this disease. The causal relationships between sedentary behavior, factors secreted by skeletal muscle at rest and during contraction and the development of T2D remain to be elucidated. Many myokines shown to influence muscle energy metabolism still have not been characterized in the context of T2D in skeletal muscle specifically. The purpose of this review is to highlight what is known and what remains to be determined regarding myokine secretion in patients with T2D to uncover potential therapeutic targets for the management of this disease.     

Subclinical vascular disease in patients with diabetes is associated with insulin resistance

Patients with diabetes experience increased cardiovascular risk that is not fully explained by deficient glycemic control or traditional cardiovascular risk factors such as smoking and hypercholesterolemia. Asymptomatic patients with diabetes show structural and functional vascular damage that includes impaired vasodilation, arterial stiffness, increased intima-media thickness and calcification of the arterial wall. Subclinical vascular injury associated with diabetes predicts subsequent manifestations of cardiovascular disease, such as ischemic heart disease, peripheral artery disease and stroke. Noninvasive detection of subclinical vascular disease is commonly used to estimate cardiovascular risk associated to diabetes. Longitudinal studies in normotensive subjects show that arterial stiffness at baseline is associated with a greater risk for future hypertension independently of established risk factors. In patients with type 2 diabetes, vascular disease begins to develop during the latent phase of insulin resistance, long before the clinical diagnosis of diabetes. In contrast, patients with type 1 diabetes do not manifest vascular injury when they are first diagnosed due to insulin deficiency, as they lack the preceding period of insulin resistance. These findings suggest that insulin resistance plays an important role in the development of early vascular disease associated with diabetes. Cross-sectional and prospective studies confirm that insulin resistance is associated with subclinical vascular injury in patients with diabetes, independently of standard cardiovascular risk factors. Asymptomatic vascular disease associated with diabetes begins to occur early in life having been documented in children and adolescents. Insulin resistance should be considered a therapeutic target in order to prevent the vascular complications associated with diabetes.     

Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study

Background and aimsType 2 diabetes mellitus (T2DM) is a condition defined by hyperglycaemia, but also often presents with dyslipidaemia and suppressed HDL cholesterol. Mendelian randomization studies have suggested a causal link between low HDL cholesterol and T2DM. However, influences of gender, polymorphisms and lifestyle, all known to influence HDL cholesterol, have not been fully explored in a prospective cohort.Methods and resultsIn 2001–2002, a random sample of 1514 males (18–87 years old) and 1528 females (18–89 years old) were recruited in the ATTICA study. The 10-year follow-up (2011–2012) included 1485 participants. Lipids and lipoproteins levels, glucose and insulin levels were measured together with apolipoprotein A1 (apoA1) 75 G/A genotype, which is known to influence HDL-cholesterol. In total, 12.9% of the study sample developed T2DM within the 10-year follow-up period. In multivariable models, for each mg/dL increase in apoA1 levels in males, 10-year T2DM risk decreased 1.02%; while every unit increase in apoB/LDL-cholesterol ratio increased risk 4-fold. Finally, for every unit increase in triglycerides/apoA1 ratio, the risk increased 85%. HOMA-IR independently predicted T2DM 10-year incidence only for carriers of GG polymorphism (all, p < 0.05), but not in carriers of the GA polymorphism (all, p > 0.05).ConclusionApoA1 was associated with decreased T2DM risk and TG/ApoA1 and apoB/LDL were associated with increased risk of T2DM, only in males. ApoA1 polymorphism, which is associated with lower HDL cholesterol, influenced the predictive effects of HOMA-IR on T2DM incidence, which appeared to be moderated by physical activity, suggesting potential scope for more targeted preventative strategies.     

Differences in taste and smell perception between type 2 diabetes mellitus patients and healthy controls

Background and aimsThe senses of taste and smell are essential determinants of food choice, which in turn may contribute to the development of chronic diseases, including diabetes. Although past studies have evaluated the relationship between type 2 diabetes mellitus (DM2) and senses disorders, this relationship remains controversial.In this study, we evaluated taste and smell perception in DM2 patients and healthy controls (HC). Moreover, we analyzed the association of chemosensory impairments with anthropometric and clinical outcomes (e.g. Body Mass Index (BMI), Fasting blood glucose (FBG), drugs, cardiovascular diseases (CVD), and hypertension) in DM2 patients.Methods and resultsThe study included 94 DM2 patients and 244 HC. Taste recognition for 6-n-propylthiouracil (PROP), quinine, citric acid, sucrose, and sodium chloride (NaCl) compounds was assessed using a filter paper method, while smell recognition of 12 odorants was performed using a Sniffin’ sticks test.We found that a higher percentage of DM2 patients showed identification impairment in salt taste (22% vs. 5%, p-value<0.0009) and smell recognition (55% vs. 27%, p-value = 0.03) compared to HC. We also observed that 65% of hypertensive DM2 subjects presented smell identification impairment compared to 18% of non-hypertensive patients (p-value = 0.019). Finally, patients with impairments in both taste and smell showed elevated FBG compared to patients without impairment (149.6 vs.124.3 mg/dL, p-value = 0.04).ConclusionThe prevalence of taste and smell identification impairments was higher in DM2 patients compared to HC, and a possible relationship with glycemic levels emerged.     

Insulin clearance is altered in women with a history of gestational diabetes progressing to type 2 diabetes

Background and aimsInsulin clearance is a relevant process in glucose homeostasis. In this observational study, we aimed to assess insulin clearance (Cl_INS) in women with former gestational diabetes (fGDM) both early after delivery and after a follow-up.Methods and resultsWe analysed 59 fGDM women, and 16 women not developing GDM (CNT). All women underwent an oral glucose tolerance test (OGTT) yearly, and an insulin-modified intravenous glucose tolerance test (IVGTT) at baseline and at follow-up end (until 7 years). Both IVGTT and OGTT Cl_INS was assessed as insulin secretion to plasma insulin ratio. We also defined IVGTT first (0–10 min) and second phase (10–180 min) Cl_INS. We found that 14 fGDM women progressed to type 2 diabetes (PROG), whereas 45 women remained diabetes-free (NONPROG). At baseline, IVGTT Cl_INS showed alterations in PROG, especially in second phase (0.88 ± 0.10 l·min⁻¹ in PROG, 0.60 ± 0.06 in NONPROG, 0.54 ± 0.07 in CNT, p ≤ 0.03). Differences in Cl_INS were not found from OGTT. Cox regression analysis showed second phase Cl_INS as significant type 2 diabetes predictor (hazard ratio = 1.90, 95% confidence interval 1.09–3.30, p = 0.02).ConclusionThis study showed that insulin clearance derived from an insulin-modified IVGTT is notably altered in women with history of GDM progressing towards type 2 diabetes.     

Associations between serum amino acids and incident type 2 diabetes in Chinese rural adults

Background and aimsSome amino acids (AAs) may be associated with type 2 diabetes (T2DM). This study aimed to determine the associations of individual AAs with the development of T2DM in rural Chinese adults.Methods and resultsA cohort study of 1199 individuals aged 18 years or older was conducted from 2006 to 2008 in a rural community of Deqing, China, a repeated survey was done in 2015 and data linkage with the electronic health records system was performed each year for identifying new T2DM cases. A high-performance liquid chromatography approach was used to measure the baseline serum concentrations of 15 AAs. Cox proportional hazards models were used to examine the associations between AAs and the risk of incident T2DM. A total of 98 new T2DM cases were identified during the follow-up of 12 years on average. Among 15 AAs, proline was associated with an increased risk of incident T2DM after adjusted for age, sex, body mass index, fasting plasma glucose, family history of T2DM, smoking status, alcohol use, and history of hypertension, the adjusted hazard ratio for 1-standard deviation increment was 1.20 (95% confidence interval: 1.00, 1.43). The association tended to be more marked in subjects younger than 60 years and overweight/obese subjects. Among participants without hypertension, proline and phenylalanine were associated with an increased risk of incident T2DM, while aspartic acid was associated with a decreased risk.ConclusionSerum proline was associated with the risk of incident T2DM in rural Chinese adults and might be a potential predictor.     

Association between PNPLA3 rs738409 variant and 5-year estimated glomerular filtration rate decline in post-menopausal women with type 2 diabetes: A panel-data analysis

Background and aimsLittle is known about the relationship between patatin-like phospholipase domain-containing protein-3 (PNPLA3) rs738409 variant and decline in estimated glomerular filtration rate (eGFR) over time in individuals with type 2 diabetes (T2DM).Methods and resultsWe enrolled an outpatient sample of 46 post-menopausal women with T2DM and preserved kidney function at baseline (in 2017), who were followed through 2022. eGFR and albuminuria were measured annually. Genotyping of PNPLA3 rs738409 was performed by TaqMan-based RT-PCR system. Overall, 25 (54.3%) patients had PNPLA3 rs738409 CC (homozygous wild-type) genotype and 21 had CG or GG genotypes. During the 5-year follow-up, the presence of rs738409 CG/GG genotypes was associated with faster eGFR decline (coefficient: −6.55; 95% CI −11.0 to −2.08; p = 0.004 by random-effects panel data analysis). This association remained significant even after adjustment for 5-year changes in age, hemoglobin A1c, hypertension status, albuminuria and use of sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists.ConclusionsThis pilot study suggests that in post-menopausal T2DM women with preserved kidney function at baseline, the risk allele (G) of PNPLA3 rs738409 is associated with a faster eGFR decline during a 5-year follow-up, independent of annual changes in common renal risk factors and use of certain glucose-lowering medications.     

CAPTURE: A cross-sectional study on the prevalence of cardiovascular disease in adults with type 2 diabetes in Italy

Background and aimsThe prevalence of type 2 diabetes (T2D) in Italy is increasing and cardiovascular disease (CVD) represents the leading cause of death in this population. CAPTURE was a multinational, multicentre, non-interventional, cross-sectional study assessing the prevalence of CVD, atherosclerotic CVD (AsCVD) and CVD subtypes among patients with T2D, across 13 countries. Here we report the results from Italy.Methods and resultsOverall, 816 patients with T2D (median age, 69 years [interquartile range: 62–75]; median duration of diabetes, 11.2 years [interquartile range: 5.7–18.7]) were recruited during routine clinical visits at secondary care centres in Italy between December 2018–September 2019. The prevalence of CVD was estimated at 38.8%, largely accounted for by AsCVD (33.1%). The most prevalent CVD subtype was coronary heart disease (20.8%), followed by carotid artery disease (13.2%). Most patients (85.9%) were prescribed oral glucose-lowering agents (GLAs), particularly biguanide (76.7%). Insulin use was higher in patients with CVD (41.3%) than in patients without CVD (32.9%). Sodium-glucose co-transporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were prescribed to 20.2% vs 14.6%, and 14.5% vs 16.6% of patients with CVD compared to those without CVD, respectively.ConclusionThe results show that, in Italy, more than one in three patients with T2D attending secondary care centres have CVD, 85% of whom have AsCVD, yet only a minority are treated with SGLT2is and GLP-1 RAs, in discordance with the recommendations of current national and international guidelines.     

Sex-specific association of BMI change with stroke in middle-aged and older adults with type 2 diabetes

Background and aimsWe aimed to evaluate the association between BMI change and stroke in middle-aged and older adults with type 2 diabetes and identify sex differences.Methods and resultsThe China Health and Retirement Longitudinal Study is an ongoing national population-based cohort study. Participants aged 45 or above with type 2 diabetes were enrolled and followed for stroke incidence. BMI change was defined as BMI at 2013-BMI at 2011. Of 1774 participants (mean [SD] age in 2011, 60.23 [8.88] years), 795 (44.8 %) were men. A total of 112 incident stroke cases were confirmed up to 2018. The incidence rate of stroke was similar between men and women (6.79 % vs 5.92 %, P = 0.516). BMI increase was independently associated with an increased stroke risk (adjusted odds ratio, 1.15; 95 % CI, 1.05–1.31) in men, while this positive association was not significant in women (adjusted odds ratio, 1.12; 95 % CI, 0.98–1.29). In addition, the positive dose–response relationship between BMI increase and stroke was observed only in men.ConclusionAmong middle-aged and older adults with type 2 diabetes, there is a sex-specific association of BMI change with stroke. An increase in BMI could result in a higher risk of incident stroke in men.     

Contribution of rare variants in monogenic diabetes-genes to early-onset type 2 diabetes

AimThis study investigated whether rare, deleterious variants in monogenic diabetes-genes are associated with early-onset type 2 diabetes (T2D).MethodsA nested case-control study was designed from 9712 Italian patients with T2D. Individuals with age at diabetes onset ≤35 yrs (n = 300; cases) or ≥65 yrs (n = 300; controls) were selected and screened for variants in 27 monogenic diabetes-genes by targeted resequencing. Rare (minor allele frequency-MAF <1%) and possibly deleterious variants were collectively tested for association with early-onset T2D. The association of a genetic risk score (GRS) based on 17 GWAS-SNPs for T2D was also tested.ResultsWhen all rare variants were considered together, each increased the risk of early-onset T2D by 65% (allelic OR =1.64, 95% CI: 1.08–2.48, p = 0.02). Effects were similar when the 600 study participants were stratified according to their place of recruitment (Central-Southern Italy, 182 cases vs. 142 controls, or Rome urban area, 118 vs. 158, p for heterogeneity=0.53). Progressively less frequent variants showed increasingly stronger effects in the risk of early-onset T2D for those with MAF <0.001% (OR=6.34, 95% CI: 1.87–22.43, p = 0.003). One unit of T2D-GRS significantly increased the risk of early-onset T2D (OR 1.09, 95% CI: 1.01–1.18; p = 0.02). This association was stronger among rare variants carriers as compared to non-carriers (p = 0.02).ConclusionRare variants in monogenic-diabetes genes are associated with an increased risk of early-onset T2D, and interact with common T2D susceptibility variants in shaping it. These findings might help develop prediction tools to identify individuals at high risk of developing T2D in early adulthood.     

Relationship between alcohol consumption and insulin resistance measured using the homeostatic model assessment for insulin resistance: A retrospective cohort study of 280,194 people

Background and aimAlcohol consumption causes metabolic disorders and is a known risk factor for cardiovascular disease. However, some studies suggested that low level alcohol consumption improves insulin resistance. We evaluated the effects of alcohol consumption on insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR).Methods and resultsThis study included 280,194 people without diabetes who underwent comprehensive health examinations more than twice between 2011 and 2018. The levels of alcohol intake were obtained through a self-questionnaire. All subjects were divided into two groups based on the Korean standard cut-off value of HOMA-IR, 2.2. Cox proportional hazard analysis was used to assess the risk of insulin resistance according to alcohol consumption. The mean age of the study subjects was 38.2 years and 55.7% were men. During the follow-up period (median 4.13 years), HOMA-IR progressed from <2.2 to ≥2.2 in 64,443 subjects (23.0%) and improved from ≥2.2 to <2.2 in 21,673 subjects (7.7%). In the parametric survival analysis, alcohol consumption was associated with improvement of HOMA-IR (HR [95% CI], 1.09[1.03–1.14], 1.11[1.06–1.17] and 1.20[1.13–1.26], respectively). In the analysis classified according to changes in alcohol consumption amounts, increased alcohol consumption tended to prevent the progression of HOMA-IR (0.97[0.96–0.99]; p = 0.004). However, the association between the changes in alcohol consumption amounts and improvement of HOMA-IR was not statistically significant.ConclusionThis retrospective observational study has shown that alcohol consumption can improve insulin resistance and increased alcohol consumption amounts may have preventive effects on the progression of HOMA-IR compared to the baseline level.     

The switch from rapid-acting to concentrated regular insulin improves glucose control in type 2 diabetes patients on pump therapy: A cohort survey

BackgroundTo evaluate the impact of switching from U-100 to U-500 insulin in patients with type 2 diabetes mellitus (T2DM) uncontrolled with continuous subcutaneous insulin infusion (CSII) by pump.MethodsWe retrospectively collected data from patients with T2DM, treated by U-100 CSII, who were switched to U-500 regular insulin where haemoglobin A1c (Hb_A1c) was >8% and/or insulin total daily dose (TDD) was >100 UI/d. Data collection from patient medical records included Hb_A1c, lipid levels, liver biomarkers, weight, TDD, declared hypoglycaemic episodes and measured by continuous glucose monitoring (CGM).ResultsSixty-five patients were included, aged 63.9 ± 8.6 years, insulin pump since 3.7 ± 3 years, TDD 186 ± 52 U/day, body mass index 39.4 ± 5.3 kg/m², Hb_A1c 9.03 ± 1.6%. After switching to U-500 insulin, Hb_A1c dropped by -0.96% (P < 0.0001) at one year with the effect maintained at three years (- 0.95%, P < 0.01). A subgroup analysis (n=42/65) using a severity score which covered the three previous years on U-100 and the next three years on U-500 insulin confirmed the latter's efficacy. Body weight increased by + 4.8 kg and TDD by 16% at three years. Declared non-severe hypoglycaemia increased significantly three- to four-fold during follow up, but % time-below-range at six months did not differ between the two treatments. Baseline Hb_A1c correlated with improved glucose control with U-500.ConclusionsU-100 to U-500 insulin switch improves glucose control in CSII T2DM patients, especially with high baseline Hb_A1c. Use of concentrated insulin in pumps may represent an advance in the strategy for treating T2DM insulin resistant states with uncontrolled hyperglycaemia after a switch from multiple daily injections to pump therapy.     

Seasonal variation in estimated cardiovascular risk in patients with type 2 diabetes

Background and aimsSeasonal variations in several risk factors for cardiovascular events (CVD) were described. Here, we evaluate the impact of seasonal variations in blood pressure (BP), lipid profile and glycemic control on estimated CVD risk in patients with type 2 diabetes (T2D).Methods and resultsRetrospective monocentric study of patients with T2D who were visited at least once in the winter period and once in the summer period, less than 8 months apart, for which data related to systolic (S) BP, diastolic (D) BP, body mass index, glycosylated hemoglobin (HbA1c), total cholesterol, HDL cholesterol and smoking habit were available on both occasions. The 10-year CVD risk was calculated using the UKPDS risk engine and the ASCVD risk estimator. As many as 411 patients were included in the study. Significant within-patient differences between summer and winter were found for the absolute risk of events assessed with both calculators (Δs-w UKPDS-CHD: ?1.33%, Δs-w UKPDS-Stroke: ?0.84%, Δs-w ASCVD: ?2.21%). The seasonal change in SBP was the main responsible for the change in risk estimated with both the UKPDS-Stroke (r² = 0.43) and the ASCVD (r² = 0.50) scores, while the change in total cholesterol was the main determinant of the change in risk for the UKPDS-CHD (r² = 0.34). A significant correlation was identified between changes in temperature and changes in SBP (ρ = 0.130, p = 0.008), but not in other risk factors.ConclusionsSeasonal variations in the classic CVD risk factors influence the risk estimated using validated calculators.     

Association between insulin resistance and incidence of carotid atherosclerotic plaque: A cohort study

Background and aimsThere is limited evidence on the association between insulin resistance (IR) and carotid plaque was reported in prospective study. We aimed to exploit the relationship between IR and carotid plaque in a prospective cohort study.Methods and resultsThe study was performed in a functional community cohort in urban Beijing. In 2015, a total of 7061 individuals without intima-media thickness (IMT) thickening and carotid artery plaque were recruited and followed up until 2019. Restricted cubic spline was conducted to exploit the dose–response relationship between carotid plaque and baseline HOMA-IR or TyG index as continuous variables. Logistic regression was used to analyze the associations between carotid plaque and HOMA-IR or TyG index. During the average 4 years follow-up, 589 subjects developed carotid plaque. Both HOMA-IR and TyG index showed significant linear dose–response relationship on carotid plaque (p < 0.001). The RRs (95%CI) for subjects with baseline HOMA-IR in quartile 2, quartile 3 and quartile 4 were 1.52 (1.14–2.04), 1.86 (1.40–2.46), and 2.55 (1.94–3.35) compared to quartile 1, respectively. Compared to the first quartile of TyG, the RRs (95%CI) for subjects in quartile 2, quartile 3 and quartile 4 were 1.43 (1.08–1.90), 1.59 (1.20–2.12), and 1.69 (1.26–2.25), respectively. In total population, the predictive ability of HOMA-IR for carotid plaque was significantly better than that of TyG index (p = 0.025).ConclusionIR is an independent risk factor of carotid plaque. Both HOMA-IR and TyG has significant predictive ability for carotid plaque.     

A deep learning model for screening type 2 diabetes from retinal photographs

Background and aimsWe aimed to develop and evaluate a non-invasive deep learning algorithm for screening type 2 diabetes in UK Biobank participants using retinal images.Methods and resultsThe deep learning model for prediction of type 2 diabetes was trained on retinal images from 50,077 UK Biobank participants and tested on 12,185 participants. We evaluated its performance in terms of predicting traditional risk factors (TRFs) and genetic risk for diabetes. Next, we compared the performance of three models in predicting type 2 diabetes using 1) an image-only deep learning algorithm, 2) TRFs, 3) the combination of the algorithm and TRFs. Assessing net reclassification improvement (NRI) allowed quantification of the improvement afforded by adding the algorithm to the TRF model. When predicting TRFs with the deep learning algorithm, the areas under the curve (AUCs) obtained with the validation set for age, sex, and HbA1c status were 0.931 (0.928–0.934), 0.933 (0.929–0.936), and 0.734 (0.715–0.752), respectively. When predicting type 2 diabetes, the AUC of the composite logistic model using non-invasive TRFs was 0.810 (0.790–0.830), and that for the deep learning model using only fundus images was 0.731 (0.707–0.756). Upon addition of TRFs to the deep learning algorithm, discriminative performance was improved to 0.844 (0.826–0.861). The addition of the algorithm to the TRFs model improved risk stratification with an overall NRI of 50.8%.ConclusionOur results demonstrate that this deep learning algorithm can be a useful tool for stratifying individuals at high risk of type 2 diabetes in the general population.     

Low serum creatinine to cystatin C ratio is independently associated with sarcopenia and high carotid plaque score in patients with type 2 diabetes

Background and aimsLow serum creatinine (Cr) to cystatin C (cysC) ratio has been suggested to be associated with low muscle mass and strength and poor prognosis in various chronic disease. We investigated the associations of CCR with sarcopenia and carotid plaque score (PS) in patients with type 2 diabetes mellitus.Methods and resultsA total of 1577 patients with type 2 diabetes were enrolled. High PS was defined as PS ≥ 3. Sarcopenia was assessed by the measurement of appendicular skeletal muscle mass (ASM) and grip strength (GS). Compared to the highest CCR group, the lowest tertile group was older; had higher C-reactive protein levels, CIMT, and PS, but lower cysC-based estimated glomerular filtration rate (cysC-eGFR), ASM/BMI, and GS. Positive correlations between CCR and ASM/BMI (r = 0.239 in men and 0.303 in women, p < 0.001) and GS (r = 0.282 in men and 0.270 in women, p < 0.001) were observed in both genders. Odds ratios and 95% confidence intervals for high PS after adjusting for age and sex were 1.22 (0.92–1.61, p = 0.18) in the middle and 1.74 (1.31–2.30, p < 0.001) in the lowest tertiles, respectively, with those of the lowest tertile remaining significant after further adjusting for multiple confounders.ConclusionsLow CCR was independently associated with sarcopenia and high PS in patients with type 2 diabetes mellitus, especially after adjusting for ASM/BMI and GS.