Cardiorespiratory Fitness and Risk of Microvascular Complications in Patients with Type 2 Diabetes Mellitus.

Heart failure (HF) is a cardiovascular disease (CVD) outcome that is associated with high morbidity and mortality as well as high healthcare costs.1 Given that HF is the end stage of most CVDs, both conditions share common risk factors such as type 2 diabetes (T2D), hypertension, smoking and obesity.2 Socioeconomic status (SES) has been recognized to have a measurable and significant effect on cardiovascular health. It has been reported that low SES may confer a cardiovascular risk that is equivalent to conventional risk factors.3 Low SES has been shown to be a powerful and independent predictor of HF development and adverse outcomes.4 Biological, behavioural and psychosocial risk factors prevalent in socioeconomically deprived individuals are known to accentuate the relationship between low SES and cardiovascular outcomes such as HF.3 These include lower levels of education, unhealthy lifestyles such as excessive alcohol consumption, limited access to health care and higher prevalence of comorbid conditions. The beneficial effects of regular physical activity (PA) and exercise in preventing vascular disease and promoting overall health are well established and documented. These benefits also extend to HF prevention.5 Though cardiorespiratory fitness (CRF) reflects habitual aerobic PA, it is a separate measure that captures the capacity of the cardiovascular and respiratory systems to supply oxygen to skeletal muscles during progressive PA or incremental exercise to volitional fatigue.6 The gold standard for CRF assessment is direct measurement of the highest attained oxygen consumption (VO2) during cardiopulmonary exercise testing. Similar to PA, high levels of CRF are strongly and independently associated with lower risk of vascular outcomes including HF.7, 8 The inverse associations between CRF and vascular outcomes have been reported to be stronger than that of traditional risk factors such as T2D and smoking; this has led to CRF being proposed as a vital sign.9 There is increasing evidence showing that higher levels of CRF can attenuate the adverse impact of other risk factors; for instance, we and others have previously shown that high CRF levels can attenuate the impact of risk factors associated with mortality,10 pneumonia11 and COVID-19 hospitalization.12 Given the evidence, we hypothesized that high CRF levels would attenuate the increased risk of HF due to low SES. To explore this, we aimed to evaluate the joint effects of SES and CRF on the risk of incident HF using a population-based prospective cohort of 1831 middle-aged Finnish men without a history of HF at baseline. We also evaluated the separate associations of SES and CRF with the risk of HF to confirm previous evidence of these associations. Reporting of the study conforms to broad EQUATOR guidelines13 and was conducted according to STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) guidelines for reporting observational studies in epidemiology (Appendix S1). The current analysis is based on the Kuopio Ischaemic Heart Disease (KIHD) risk factor study, a general population-based prospective cohort study comprising of a representative sample of men aged 42–61 years recruited in eastern Finland. A detailed description of the study design, recruitment methods, risk marker assessment and physical examinations have been described previously.8 Baseline measurements were performed between 01 March 1984 and 31 December 1989. The research protocol was approved by the Research Ethics Committee of the University of Eastern Finland and written informed consent was obtained from all the participants. A self-reported questionnaire was used to assess SES, which involved a summary index that combined factors such as income, education, occupational prestige, material standard of living and housing conditions. The composite SES index ranged from 0 to 25, with higher values indicating lower SES. Maximal oxygen uptake (VO2max) was used as a measure of CRF, which was assessed using a respiratory gas exchange analyser (Medical Graphics, MCG, St. Paul, Minnesota) during cycle ergometer exercise testing.14 We excluded men with a prevalent history of HF for the current analysis. We included all HF events that occurred from study entry through to 2018. The diagnostic classification of HF cases was coded according to the ICD-10 codes. Hazard ratios (HRs) with 95% confidence intervals (CIs) for HF were calculated using Cox proportional hazard models and these were adjusted for in three models: (Model 1) age; (Model 2) Model 1 plus systolic blood pressure (SBP), body mass index (BMI), heart rate, smoking status, history of T2D, history of coronary heart disease (CHD), total cholesterol, high-density lipoprotein cholesterol (HDL-C) and PA; and (Model 3) Model 2 plus mutual adjustment for each exposure. For consistency with previous reports,10, 15 the exposures (SES and CRF) were categorized into low and high levels based on their median cutoffs. The exposures were also modelled as continuous variables given evidence of linear relationships with HF risk using multivariable restricted cubic spline curves. Evaluation of the joint association of SES and CRF with HF risk was based on the following four combinations: high SES-low CRF; low SES- low CRF; high SES-high CRF and low SES-high CRF. Tests of interaction were used to formally assess if the risk of HF due to one exposure is modified by the other exposure and vice versa. To put our findings into clinical context, we also calculated the number needed to treat (NNT) associated with high SES-high CRF using the formula proposed by Altman and Anderson16: NNT (t) =1/[SB(t))HR – SB(t)], where SB(t) denotes the Kaplan–Meir survival probability in the reference group (High SES-Low CRF) at time t and HR refers to the Cox regression estimate comparing the exposure group with the reference group. Stata version MP 16 (Stata Corp, College Station) was employed for all analyses. The overall mean (standard deviation, SD) age, SES and CRF of study participants at baseline was 52 (5) years, 8.26 (4.24) and 30.8 (7.9) ml/kg/min, respectively (Table 1). There were significant differences in baseline characteristics between low and high CRF groups. Overall Mean (SD) or median (IQR) or n (%) High CRF Mean (SD) or median (IQR) or n (%) Low CRF Mean (SD) or median (IQR) or n (%) During a median (interquartile range) follow-up of 27.3 (18.6–31.2) years, 364 incident HF cases occurred. In an analysis adjusted for age, SBP, BMI, heart rate, smoking status, history of T2D, history of CHD, total cholesterol, HDL-C and PA, low compared with high SES was associated with an increased risk of HF 1.43 (95% CI: 1.15–1.79), which remained similar on further adjustment for CRF. On adjustment for the confounders as above, high CRF was associated with a decreased risk of HF compared with low CRF 0.70 (95% CI: 0.55–0.89), which remained similar on additional adjustment for SES. There was evidence of significant associations when both exposures were modelled as continuous variables (Table 2). Restricted cubic spline curves with adjustment for age, SBP, BMI, heart rate, smoking status, history of T2D, history of CHD, total cholesterol, HDL-C and PA showed that HF risk increased continuously with decreasing SES across the range 7–19 (p-value for nonlinearity =.83) (Figure 1A), whereas HF risk decreased continuously with increasing CRF across the range 18–58 ml/kg/min (p-value for nonlinearity =.79) (Figure 1B). The spline curves were qualitatively similar in subgroups of CRF and SES (Figure 2). In multivariable analysis, low SES-low CRF was associated with an increased HF risk 1.32 (95% CI: 1.01–1.74), high SES-high CRF with a decreased HF risk 0.62 (95% CI: 0.43–0.89), with no evidence of an association for low SES-high CRF and HF risk 1.01 (95% CI: 0.73–1.39) when compared with men with high SES-low CRF (Table 2). The association of SES with HF risk was not modified by CRF (p-value for interactions >.10) and neither was the association between CRF and HF risk modified by SES (p-value for interactions >.10), when both exposures were modelled as continuous or categorical variables (Figure 3). The absolute risk reduction of HF associated with high SES-high CRF was 0.21 during the entire duration of follow-up, which translated into a NNT of 10 (95% CI: 6–35) to prevent one HF. Our results based on a general population-based prospective cohort study of middle-aged to older Finnish men confirms the previously reported independent associations of low SES with increased HF risk and high CRF levels with lowered risk of HF. The associations were also potentially consistent with graded dose-response relationships. Evaluation of the joint associations of SES and CRF with HF risk showed that increased CRF levels appeared to attenuate the increased risk of HF associated with low SES. However, formal tests showed no significant evidence of interactive effects of SES and CRF on the long-term risk of HF, suggesting the effect of each exposure on HF risk may be independent of the other. Given the low sample size and event rates in the exposure categories, studies with larger samples are needed to confirm or refute potential interactive effects of SES and CRF on HF risk. Finally, our findings suggest that the NNT for high aerobic fitness levels and high SES to prevent a HF event over long-term follow-up ranged from 6 to 35 in approximately healthy middle-aged to older men. The interaction between SES and HF has been reported to be complex and the precise mechanisms accounting for the association between low SES and increased HF risk remain elusive.4 Socioeconomic differences in potential aetiological risk factors such as alcohol consumption, hypertension and systemic inflammation, have been reported to contribute to the risk. Social deprivation is also associated with lower rates of treatment, dose and adherence to therapy for, and delayed presentation of hypertension, diabetes and CHD,4 which consequently lead to HF. Psychosocial factors such as stress and depression, which are strongly associated with cardiovascular outcomes, also disproportionately affect individuals of low SES.3 Though CRF is determined by many non-modifiable factors such as age, sex and heritability, it remains a modifiable risk factor. The most established methods of increasing CRF are via exercise training and increased PA.9 Greater PA and exercise reduce HF risk through various mechanisms including (i) reducing the prevalence of standard and novel cardiovascular risk factors such as hypertension, obesity, blood glucose and coronary artery disease; (ii) preventing adverse changes in cardiac structure and function; (iii) promoting physiologic remodelling and (iv) improving cardiac, neurohormonal, skeletal muscle, pulmonary, renal and vascular performance.5 These findings may have important clinical implications. They add to the overwhelming evidence on the benefits of high CRF levels (via regular aerobic PA) on chronic diseases and their potential ability to attenuate the adverse effects of traditional risk factors. Despite guideline recommendations and population-wide strategies to promote PA levels, most populations do not achieve general PA recommendations. Populations at high cardiovascular risk including the socioeconomically deprived need more education on the substantial benefits of PA. Furthermore, there should be widened access to PA resources that are both feasible and attractive for these populations. This is the first evaluation of the separate and joint associations of SES and CRF with HF risk. We also assessed the nature of the dose-response relationships of the exposures with HF risk. Other strengths of this analysis included the use of a prospective cohort design with exclusion of men with pre-existing HF, the long-term follow-up duration of the cohort and the use of a gold standard measure of CRF. Limitations deserving consideration included the relatively low sample size due to the categorization of exposures, use of self-administered questionnaires in assessing SES, findings may only be generalizable to middle-aged and older northern European men and potential for biases such as residual confounding and regression dilution bias. In a general male Finnish population, both SES and CRF were each independently associated with HF risk, potentially consistent with graded dose-response relationships. High levels of CRF may attenuate the increased risk of HF due to low SES, but further study is needed to confirm if there are true interactive effects of SES and CRF on the long-term risk of HF. The authors thank the staff of the Kuopio Research Institute of Exercise Medicine and the Research Institute of Public Health and University of Eastern Finland, Kuopio, Finland for the data collection in the study. J.A.L. acknowledges support from The Finnish Foundation for Cardiovascular Research, Helsinki, Finland. These sources had no role in design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. No potential conflict of interest was reported by the authors. S.K.K.: Study design, data analysis and interpretation, drafting manuscript, and revising manuscript content and approving final version of manuscript; S.Y.J.: Study design and revising manuscript content and approving final version of manuscript; T.H.M: Study design and revising manuscript content and approving final version of manuscript; J.A.L.: Study design and conduct, responsibility for the patients and data collection, and revising manuscript content and approving final version of manuscript. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. 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To investigate the association between various obesity indices and the risk of developing microvascular complications in adult patients with Type 2 diabetes(T2DM), using cohort data derived from Yinzhou District Health Big Data Platform of China. This study included adult patients with type 2 diabetes(T2DM) who were enrolled between January 1, 2008, and December 31, 2013, in Yinzhou District, Ningbo, and did not have any microvascular complications at baseline. Data collection encompassed demographic characteristics, lifestyle behaviors, laboratory test result, and physical examination findings, obtained at both baseline and during follow-up periods through structured epidemiological surveys and clinical assessments. Various obesity indices were calculated, including body mass index(BMI), waist-to-height ratio(WHtR), a body shape index(ABSI) and body roundness index(BRI). We also computed the coefficients of variation for these obesity indices during the follow-up period. A Cox proportional hazards regression model was used to analyze the association between obesity indices at baseline and follow-up, and the risk of developing microvascular complications. Additionally, receiver operating characteristic(ROC) curves were used to analyze the predictive efficacy of the coefficients of variation for BMI, WHtR, ABSI and BRI in relation to microvascular complications, and the areas under the curve(AUCs) were calculated. A total of 27 635 patients with type 2 diabetes(T2DM) were included, contributing to 153 717 person-years of follow-up. During this period, 12 969 new cases of microvascular complications were identified, resultsing in an incidence rate of 84.37 cases per 1000 person-years. Patients were categorized into two groups based on the occurrence of complications: those with microvascular complications and those without. There was no significant difference in blood glucose levels between the two groups at baseline. After adjusting for sociodemographic characteristics, laboratory indicators, and potential confounders such as a history of hypertension and hyperlipidemia, it was found that only the WHtR(HR=1.027, 95%CI 1.008-1.046), ABSI(HR=1.035, 95%CI 1.018-1.053) and BRI(HR=1.030, 95%CI 1.011-1.049) were independently associated with the risk of microvascular complications at baseline, while waist circumference(HR=1.010, 95%CI 0.992-1.029) and BMI(HR=0.985, 95%CI 0.967-1.002) were not significantly related(P>0.05). During the follow-up period, the coefficients of variation for all obesity indices were independently associated with an increased risk of microvascular complications. Among them, abdominal obesity indices, such as waist circumference(HR=0.063, 95%CI 1.057-1.069), WHtR(HR=1.060, 95%CI 1.054-1.066), and ABSI(HR=1.062, 95%CI 1.058-1.066), were most strongly linked to the risk of microvascular complications. Further stratified analysis based on baseline BMI revealed that the variability in abdominal obesity indices was more strongly associated with microvascular complications in patients with normal and overweight BMI compared to those with obesity. Specifically, the following result were observed: waist circumference(HR_(normal BMI)=1.074, HR_(overweight)=1.059, HR_(obesity)=1.041; P<0.01), WHtR(HR_(normal BMI)=1.069, HR_(overweight)=1.059, HR_(obesity)=1.037; P<0.01), ABSI(HR_(normal BMI)=1.065, HR_(overweight)=1.067, HR_(obesity)=1.038; P<0.01), BRI(HR_(normal BMI)=1.023, HR_(overweight)=1.020, HR_(obesity)=1.011; P<0.01). Additionally, to further explore the predictive value of various obesity indices for microvascular complications in type 2 diabetes mellitus(T2DM), we conducted stratified analyses based on sex and age(using 60 years as the cutoff). WHtR showed similar predictive performance between men(AUC = 0.794) and women(AUC=0.789). However, WHtR demonstrated stronger predictive ability in individuals over 60 years old(AUC = 0.803) compared to those aged 60 years or younger(AUC = 0.777). ABSI exhibited a higher predictive value in men(AUC = 0.752) than in women(AUC = 0.730), and again, the index performed better in the older population(AUC = 0.761) than in the younger group(AUC = 0.725). Similarly, BRI demonstrated comparable performance between sexes [men(AUC = 0.796) and women(AUC = 0.791)] with the highest predictive accuracy seen in participants over 60 years(AUC = 0.806). By contrast, BMI showed relatively lower predictive power across all subgroups. Specifically, the AUC values for BMI were 0.744 in men and 0.714 in women, 0.714 in those aged 60 years or below and 0.748 in those above 60 years. Increased baseline abdominal obesity indices(WHtR, ABSI and BRI) and higher variability in obesity indices during follow-up are strongly associated with increased risks of microvascular complications in T2DM patients. In individuals with normal BMI, higher variability in abdominal obesity indices is positively correlated with the risk of microvascular complications. Furthermore, the variability in abdominal obesity indices(WHtR, ABSI and BRI) provides better predictive ability for microvascular complications compared to general obesity indices(BMI), especially in male patients and those aged over 60.

Cardiorespiratory fitness (CRF) levels appear to be an important risk factor for cancer incidence and death. To examine CRF and prostate, colon, and lung cancer incidence and mortality in Swedish men, and to assess whether age moderated any associations between CRF and cancer. A prospective cohort study was conducted in a population of men who completed an occupational health profile assessment between October 1982 and December 2019 in Sweden. Data analysis was performed from June 22, 2022, to May 11, 2023. Cardiorespiratory fitness was assessed as maximal oxygen consumption, estimated using a submaximal cycle ergometer test. Data on prostate, colon, and lung cancer incidence and mortality were derived from national registers. Hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards regression. Data on 177 709 men (age range, 18-75 years; mean [SD] age, 42 [11] years; mean [SD] body mass index, 26 [3.8]) were analyzed. During a mean (SD) follow-up time of 9.6 (5.5) years, a total of 499 incident cases of colon, 283 of lung, and 1918 of prostate cancer occurred, as well as 152 deaths due to colon cancer, 207 due to lung cancer, and 141 deaths due to prostate cancer. Higher levels of CRF (maximal oxygen consumption as milliliters per minute per kilogram) were associated with a significantly lower risk of colon (HR, 0.98, 95% CI, 0.96-0.98) and lung cancer (HR, 0.98; 95% CI, 0.96-0.99) incidence, and a higher risk of prostate cancer incidence (HR, 1.01; 95% CI, 1.00-1.01). Higher CRF was associated with a lower risk of death due to colon (HR, 0.98; 95% CI, 0.96-1.00), lung (HR, 0.97; 95% CI, 0.95-0.99), and prostate (HR, 0.95; 95% CI, 0.93-0.97) cancer. After stratification into 4 groups and in fully adjusted models, the associations remained for moderate (>35-45 mL/min/kg), 0.72 (0.53-0.96) and high (>45 mL/min/kg), 0.63 (0.41-0.98) levels of CRF, compared with very low (<25 mL/min/kg) CRF for colon cancer incidence. For prostate cancer mortality, associations remained for low (HR, 0.67; 95% CI, 0.45-1.00), moderate (HR, 0.57; 95% CI, 0.34-0.97), and high (HR, 0.29; 95% CI, 0.10-0.86) CRF. For lung cancer mortality, only high CRF (HR, 0.41; 95% CI, 0.17-0.99) was significant. Age modified the associations for lung (HR, 0.99; 95% CI, 0.99-0.99) and prostate (HR, 1.00; 95% CI, 1.00-1.00; P < .001) cancer incidence, and for death due to lung cancer (HR, 0.99; 95% CI, 0.99-0.99; P = .04). In this cohort of Swedish men, moderate and high CRF were associated with a lower risk of colon cancer. Low, moderate, and high CRF were associated with lower risk of death due to prostate cancer, while only high CRF was associated with lower risk of death due to lung cancer. If evidence for causality is established, interventions to improve CRF in individuals with low CRF should be prioritized.

High cardiorespiratory fitness (CRF) is associated with a reduced risk of Type 2 diabetes mellitus (T2DM) and improved β-cell function; genetic factors also determine these risks. This cross-sectional study investigated whether CRF modifies the association of polygenic risk of T2DM with glucose metabolism in nondiabetic Japanese men. Fasting plasma glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured in 174 Japanese men (age: 20-79 yr). β-Cell function and insulin resistance were evaluated by calculating HOMA-β and HOMA-IR, respectively. CRF was assessed by measuring maximal oxygen uptake (V̇o2max). Subjects were divided into the low and high CRF groups within each age group according to the median V̇o2max. Eleven single nucleotide polymorphisms (SNPs) associated with T2DM were analyzed and used to calculate genetic risk score (GRS); subjects were divided into the low, middle, and high GRS groups. The high GRS group had higher HbA1c levels than the low GRS group in both the low and high CRF groups (P < 0.05). Furthermore, the individuals with a high GRS had a lower HOMA-β than those with a low GRS regardless of CRF (P < 0.05). In multiple linear regression analysis, although GRS was a significant predictor of HbA1c (β = 0.153, P = 0.025), V̇o2max was also associated with HbA1c (β = -0.240, P = 0.041) independent of GRS. These results suggest that CRF is associated with HbA1c levels independent of GRS derived from T2DM-related SNPs; however, it does not modify the association of GRS with increased HbA1c or impaired β-cell function.

Association of sleep patterns with microvascular complications in individuals with type 2 diabetes: A prospective cohort study.

Many studies have indicated that high cardiorespiratory fitness (CRF) is associated with a lower risk of developing type 2 diabetes mellitus (T2DM). Although CRF changes over the long-term, the influence of duration on the association between CRF and the incidence of T2DM is not clear. PURPOSE: To investigate the influence of follow-up period on the association between CRF and the incidence of T2DM among Japanese males. METHODS: This study was conducted in 7,840 nondiabetic male workers, aged 19 to 60 years (median age 37 years) at baseline, enrolled in 1986. Participants were given a submaximal exercise test, a medical examination, and questionnaires on their health habits in 1986. CRF was measured using a cycle ergometer and maximal oxygen uptake was estimated. During 1986-2009, participants were followed for development of T2DM, which was diagnosed from annual health checkups. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) for the incidence of T2DM were estimated using Cox proportional hazards models. RESULTS: During a median of 19 years of the follow-up, 1,054 men developed T2DM. After adjustment for age, BMI, systolic blood pressure, cigarette smoking, alcohol intake, and family history of diabetes, the HRs (95%CIs) of developing T2DM across quartiles of CRF (lowest to highest) were 1.00 (reference), 0.87 (0.75-1.01), 0.77 (0.65-0.92), and 0.58 (0.47-0.71) (P for trend < 0.001). In analysis by follow-up period (1986-1993, 1994-2001, 2002-2009), the HRs (95%CIs) were 1.00 (reference), 0.85 (0.66-1.10), 0.78 (0.58-1.04), and 0.68 (0.48-0.95) (P for trend = 0.014) for 1986-1993, 1.00 (reference), 0.86 (0.67-1.09), 0.76 (0.59-0.99), and 0.57 (0.41-0.78) (P for trend < 0.001) for 1994-2001, 1.00 (reference), 0.99 (0.73-1.35), 0.78 (0.55-1.12), and 0.46 (0.29-0.72) (P for trend = 0.001) for 2002-2009, respectively. CONCLUSIONS: These results suggest that high CRF is associated with a lower risk of developing T2DM over a long-term period in Japanese men.

The association between monocyte chemoattractant protein-1 (MCP-1) -2518G/A gene polymorphism and the risk of nephropathy in type 2 diabetes mellitus (T2DM) remains controversial. A meta-analysis was conducted to assess the association of MCP-1 -2518G/A gene polymorphism with the risk of nephropathy in T2DM. Eight studies were included in our meta-analysis by searching electronic databases according to predefined criteria. No significant association between G allele, GG genotype, or AA genotype and the onset of nephropathy in T2DM was observed among Asians. GA genotype was significantly associated with nephropathy risk in T2DM among Asians (p = 0.024). MCP-1 -2518G/A gene polymorphism was not associated with nephropathy risk in T2DM among Chinese, Koreans, and Turks. For Indians, G allele and AA genotype were not associated with nephropathy risk in T2DM, GG genotype was associated with a lower risk of nephropathy in T2DM (p = 0.017), GA genotype was associated with the susceptibility of nephropathy in T2DM (p = 0.029). In conclusions, GA genotype might be a risk factor for the onset of nephropathy in T2DM among Asians, particularly Indians; GG genotype seems to be a protective factor against the susceptibility of nephropathy in T2DM among Indians.

BackgroundGlucosamine is a widely used supplement for treating osteoarthritis and joint pain. New evidence suggests a potential association between glucosamine and type 2 diabetes, inflammation and cardiometabolic risk. We aimed to prospectively evaluate the association of habitual glucosamine use with risk of diabetic microvascular complications based on data from the large-scale nationwide prospective UK Biobank cohort study.MethodsThis analysis included 21,171 participants with type 2 diabetes who were free of microvascular complications from the UK Biobank. Incidence of diabetic microvascular complications was ascertained via electronic health records. The Cox proportional hazards model was used to assess the relationship between glucosamine use and the risk of diabetic microvascular complications. Subgroup analyses and sensitivity analyses were performed to explore the potential effect modifications and the robustness of the main findings.ResultsAt baseline, 14.5% of the participants reported habitual use of glucosamine supplements. During a median follow-up of 12.3 years, 4399 people developed diabetic microvascular complications, including 2084 cases of incident diabetic nephropathy, 2401 incident diabetic retinopathy, and 831 incident diabetic neuropathy. Glucosamine use was significantly associated with lower risks of composite microvascular complications (hazard ratio (HR) 0.89, 95% CI: 0.81 to 0.97) and diabetic nephropathy (HR 0.87, 95% CI: 0.76 to 0.98) in fully adjusted models. However, there was no significant inverse association between glucosamine use and the risk of diabetic retinopathy (HR 0.94, 95% CI: 0.83 to 1.06) or diabetic neuropathy (HR 0.88, 95% CI: 0.71 to 1.08).ConclusionsHabitual use of glucosamine supplement was significantly associated with lower risks of composite microvascular complications and diabetic nephropathy but not retinopathy or neuropathy in individuals with type 2 diabetes.

BackgroundThe influence of overall lifestyle behaviors on diabetic microvascular complications remains unknown. In addition, the potential mediating biomarkers underlying the association is unclear. This study aimed to examine the associations of the combined lifestyle factors with risks of total and individual microvascular complications among patients with type 2 diabetes (T2D) and to explore the potential mediation effects of metabolic biomarkers.Methods and findingsThis retrospective cohort study included 15,104 patients with T2D free of macro- and microvascular complications at baseline (2006 to 2010) from the UK Biobank. Healthy lifestyle behaviors included noncurrent smoking, recommended waist circumference, regular physical activity, healthy diet, and moderate alcohol drinking. Outcomes were ascertained using electronic health records. Over a median of 8.1 years of follow-up, 1,296 cases of the composite microvascular complications occurred, including 558 diabetic retinopathy, 625 diabetic kidney disease, and 315 diabetic neuropathy, with some patients having 2 or 3 microvascular complications simultaneously. After multivariable adjustment for sociodemographic characteristics, history of hypertension, glycemic control, and medication histories, the hazard ratios (95% confidence intervals (CIs)) for the participants adhering 4 to 5 low-risk lifestyle behaviors versus 0 to 1 were 0.65 (0.46, 0.91) for diabetic retinopathy, 0.43 (0.30, 0.61) for diabetic kidney disease, 0.46 (0.29, 0.74) for diabetic neuropathy, and 0.54 (0.43, 0.68) for the composite outcome (all Ps-trend ≤0.01). Further, the population-attributable fraction (95% CIs) of diabetic microvascular complications for poor adherence to the overall healthy lifestyle (<4 low-risk factors) ranged from 25.3% (10.0%, 39.4%) to 39.0% (17.7%, 56.8%). In addition, albumin, HDL-C, triglycerides, apolipoprotein A, C-reactive protein, and HbA1c collectively explained 23.20% (12.70%, 38.50%) of the associations between overall lifestyle behaviors and total diabetic microvascular complications. The key limitation of the current analysis was the potential underreporting of microvascular complications because the cases were identified via electronic health records.ConclusionsAdherence to overall healthy lifestyle behaviors was associated with a significantly lower risk of microvascular complications in patients with T2D, and the favorable associations were partially mediated through improving biomarkers of glycemic control, systemic inflammation, liver function, and lipid profile.

Body mass index (BMI) might fail to distinguish between fat and muscle mass. The fat-to-muscle mass ratio (FMR) and cardiorespiratory fitness (CRF) may provide complementary insights into the risk of type 2 diabetes mellitus (T2DM). This study aimed to investigate the independent and joint associations of FMR and CRF with incident T2DM. This prospective analysis included 60 837 adults from the UK Biobank without diabetes at baseline. FMR was assessed via bioelectrical impedance analysis, and CRF was estimated from a submaximal cycle test. Cox proportional hazards models evaluated associations with T2DM incidence. Additive and multiplicative interaction effects were further estimated. Predictive performance was evaluated using time-dependent ROC analysis. Over a median 14.49-year follow-up, 2439 participants developed T2DM. Higher FMR (per 1-SD) was independently associated with higher T2DM risk in women (HR = 1.17, 95%CI: 1.07-1.27) and men (HR = 1.32, 95%CI: 1.23-1.42). Higher CRF (per 1-MET increment) was associated with lower risk in women (HR = 0.84, 95%CI: 0.80-0.89) and men (HR = 0.82, 95%CI: 0.79-0.86). Participants with both high FMR and low CRF had the highest risk (HR = 1.81, 95%CI: 1.59-2.07). This association was strongest in adults <60 years. Adding FMR and CRF to the Cambridge Diabetes Risk Score significantly improved predictive accuracy at 3, 5 and 10 years. FMR and CRF were independent predictors of T2DM, with their combination identifying the highest-risk phenotype. Integrating FMR and CRF assessment enhances T2DM risk stratification and identifies high-risk individuals who may benefit from lifestyle interventions focusing on improving body composition and fitness.

BackgroundRheological disorders of red blood cells (RBC) and decreased RBC deformability have been involved in the development of diabetic microangiopathy. However, few studies have evaluated the association of RBC count with microvascular complications in patients with type 2 diabetes mellitus (T2DM). The purpose of this study was to investigate the association of RBC count with microvascular complications in patients with T2DM.MethodsThis study involved 369 patients with T2DM: 243 with one or more microvascular complications and 126 without microvascular complications. Anticoagulated blood was collected and analyzed in an automated blood cell counter. The presence of risk factors for microvascular complications was determined.ResultsThe proportion of patients with microvascular complications increased as the RBC count decreased (P < 0.001). After adjustment for known risk factors for microvascular complications by logistic regression analysis, lower quartiles of RBC count were associated with a higher risk of microvascular complications compared with the reference group composed of the highest quartile (first quartile, odds ratio 4.98, 95% confidence interval 1.54–6.19, P = 0.008; second quartile, odds ratio 3.21, 95% confidence interval 1.17–5.28, P = 0.024).ConclusionA decreased RBC count is associated with microvascular complications in Chinese patients with T2DM. The RBC count is a potential marker to improve further the ability to identify diabetic patients at high risk of microvascular complications.

The treatment of diabetes mellitus generally involves genetically engineered human insulin (GICH) or genetically engineered analogues of human insulin (AIC). Compared to GICH, AIC better physiologically mimics endogenous insulin functionally. It would thus be logical to assume that long-term (multi-year) application of AIC leads to a lower incidence of diabetic angiopathy compared to GICH. To date, however, no long-term comparisons of both classes of insulin preparations (in terms of efficacy of glycemic control or incidence of microvascular complications in patients with type 1 diabetes) have been performed.&#x0D; Aims. To retrospectively compare the efficacy of glycemic control and incidence of microvascular complications (nephropathy and retinopathy) in patients with type 1 diabetes treated for at least 10 years with either GICH or AIC.&#x0D; Materials and methods. Based on data from electronic databases (diabetes registry) from several regions within the Russian Federation, the following patient samples were examined (n=260): group 1 received GICH for 10 years (n = 130) and group 2 received AIC for 10 years (n = 130). Patients in both groups underwent pairwise matching for baseline clinical characteristics (sex, age of diabetes onset, duration of disease and HbA1clevel). All patients were observed by endocrinologists in the clinic.&#x0D; Results. After 10 years of follow up, HbA1с levels declined more significantly in group 2 than in group 1 (1.30% vs. 0.81%, respectively, P 0.05). By the end of the observation period, the presence of diabetic retinopathy (any stage) increased in both groups and was not significantly different between groups; the presence of diabetic nephropathy was also increased in both groups, but the increase was significantly lower in group 2 than in group 1 (20.5% vs. 33.9%, respectively, P 0.05). Overall, the risk of microvascular complications was significantly higher in group 1 than in group 2 [HR (hazard ratio): 1.84; 95% CI: 1.372.48), specifically, the risk of diabetic retinopathy (HR: 1.37; 95% CI: 0.981.90).&#x0D; Conclusions. A 10-year retrospective analysis of patients treated with AIC for type 1 diabetes in the clinic showed a significantly more effective reduction in HbA1c levels and a lower incidence of diabetic nephropathy, compared with patients treated with GICH.

BackgroundA higher resting heart rate is associated with an increased probability of cardiovascular complications and premature death in patients with type 2 diabetes mellitus. The impact of heart rate on the risk of developing microvascular complications, such as diabetic retinopathy and nephropathy, is, however, unknown. The present study tests the hypothesis that a higher resting heart rate is associated with an increased incidence and a greater progression of microvascular complications in patients with type 2 diabetes mellitus.Methods and ResultsThe relation between baseline resting heart rate and the development of a major microvascular event was examined in 11 140 patients who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study. Major microvascular events were defined as a composite of new or worsening nephropathy or new or worsening retinopathy. Patients with a higher baseline heart rate were at increased risk of a new major microvascular complication during follow-up (adjusted hazard ratio: 1.13 per 10 beats per minute; 95% confidence interval: 1.07–1.20; P<0.001). The excess hazard was evident for both nephropathy (adjusted hazard ratio: 1.16 per 10 beats per minute; 95% confidence interval: 1.08–1.25) and retinopathy (adjusted hazard ratio: 1.11 per 10 beats per minute; 95% confidence interval: 1.02–1.21).ConclusionPatients with type 2 diabetes mellitus who have a higher resting heart rate experience a greater incidence of new-onset or progressive nephropathy and retinopathy.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00145925. http://www.advance-trial.com/static/html/prehome/prehome.asp

Although the benefit of high cardiorespiratory fitness (CRF) for the prevention of type 2 diabetes mellitus (T2DM) is widely accepted, whether consistently high CRF is necessary or transiently high CRF is sufficient is unclear. The present study was conducted to examine the hypothesis that consistently high level of CRF is more beneficial than transiently high CRF for the prevention of T2DM. This cohort study was conducted in nondiabetic 7158 men age 20 to 60 yr, enrolled from 1986 to 1987. The area under the curve with respect to ground (AUCG) for CRF measurements during an 8-yr measurement period (1979-1987) was calculated as an index of integrated CRF level during the period. The differences (ΔAUCP) between AUCG and peak AUC (peak CRF-measurement period) was also calculated as an index of the presence and the size of a "spike" in CRF. T2DM was defined by fasting blood glucose and a self-reported diagnosis of diabetes for participants with blood tests. For participants without blood tests, T2DM was defined by the result of oral glucose test after a nonfasting urinary test and a self-reported diagnosis of diabetes. T2DM was determined on health checkups until 2009. During the follow-up period, 1495 men developed T2DM. After adjustment for confounders, as compared with the first quartile of AUCG for CRF, the hazard ratio (95% confidence interval) for the second, third, and fourth quartiles were 0.87 (0.76 to 1.00), 0.80 (0.68 to 0.95), and 0.72 (0.58 to 0.89), respectively. For CRF spike, there was no association between ΔAUCP in CRF and the incidence of T2DM. Consistently higher level of CRF over time was associated with lower risk of T2DM.

Background Type 2 diabetes mellitus (T2DM) is a prevalent chronic condition characterized by hyperglycemia, which can lead to various microvascular complications, including diabetic nephropathy, neuropathy, and retinopathy. Identifying reliable biomarkers for early detection and risk stratification of these complications is crucial for improving patient outcomes. Adenosine deaminase (ADA) and HbA1c have emerged as potential markers associated with immune function, inflammation, and long-term glycemic control. This study investigates the correlation between ADA and HbA1c levels and microvascular complications in patients with T2DM. Material and methods This prospective observational cross-sectional study involved 150 patients diagnosed with T2DM, focusing on those with diabetic nephropathy, neuropathy, and retinopathy. Clinical data were collected through patient interviews, clinical examinations, and laboratory tests, including measurements of fasting blood glucose, HbA1c, serum creatinine, ADA levels, and urine protein creatinine ratio (UPCR). Fundus examinations and nerve conduction velocity (NCV) tests were performed to assess diabetic retinopathy and neuropathy, respectively. Data were analyzed using SPSS version 25.0 (IBM Corp., Armonk, New York), with statistical tests to evaluate the correlation between ADA and HbA1c levels and microvascular complications. Results The study found a significant correlation between elevated ADA and HbA1c levels and microvascular complications in patients with T2DM. Higher ADA levels were particularly associated with diabetic nephropathy (p=0.003), while HbA1c levels showed a positive correlation with all three complications: nephropathy, neuropathy, and retinopathy. The findings suggest that ADA and HbA1c levels can serve as valuable biomarkers for identifying patients at higher risk of developing these complications. Conclusion This study highlights the potential of ADA and HbA1c as biomarkers for early detection and risk assessment of microvascular complications in T2DM patients. Routine monitoring of these markers could improve the management and prognosis of diabetic patients by enabling timely interventions to prevent or mitigate the progression of complications. Further research is needed to explore the underlying mechanisms linking ADA with diabetic complications and to validate its clinical utility.