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Poor quality of drug prescribing in older persons is often associated with increased drug-related adverse events, hospitalization, and mortality. The present study describes a set of prescribing quality indicators developed by the Geriatrics Working Group of the Italian Medicines Agency (AIFA) and estimates their prevalence in the entire elderly (≥ 65 years) population in Italy.We performed a cross-sectional study using 2011 data from the OsMed (Osservatorio dei Medicinali) database, which comprises all prescribed drugs that are reimbursed by the Italian National Healthcare System. Yearly prevalence of drug prescribing quality indicators in the Italian older population (n = 12,301,537) was determined.Overall, 13 quality indicators addressing polypharmacy, adherence to treatment of chronic diseases, prescribing cascade, undertreatment, drug-drug interactions, and drugs to be avoided were identified. Polypharmacy was common, with more than 1.3 million individuals taking greater than or equal to 10 drugs (11.3% of the study population). The prevalence of low adherence and undertreatment was also elevated and increased with advancing age, with highest prevalence occurring in individuals aged 85 years and older. Prevalence was less than 3% for quality indicators assessing the prescribing cascade, drug-drug interactions, and drugs to be avoided.These results confirm the high frequency of suboptimal drug prescribing in older adults, using a database that covers the whole Italian population. In general, this descriptive study may help in prioritizing strategies aimed at improving the quality of prescribing in elderly population.

The precise cause of sarcopenia, skeletal muscle loss and strength, in older persons is unknown. However, there is a strong evidence for muscle loss due to insulin resistance as well as mitochondrial dysfunction over aging. Considering that epidemiological studies have underlined that insulin resistance may have a specific role on skeletal muscle fibre atrophy and mitochondrial dysfunction has also been extensively shown to have a pivotal role on muscle loss in older persons, a combined pathway may not be ruled out. Considering that there is growing evidence for an insulin-related pathway on mitochondrial signaling, we hypothesize that a high degree of insulin resistance will be associated with the development of sarcopenia through specific alterations on mitochondrial functioning. This paper will highlight recent reviews regarding the link between skeletal muscle mitochondrial dysfunction and insulin resistance. We will specifically emphasize possible steps involved in sarcopenia over aging, including potential biomolecular mechanisms of insulin resistance on mitochondrial functioning.

Associations between copper to zinc ratio (CZr) and mortality have suggested CZr as a biomarker of aging. Nevertheless, very limited data exist on the association between serum CZr and physical or functional status of very old people. We examined the relationship between serum CZr and physical performance, muscle strength, functional status, and survival from the ilSIRENTE Study: a longitudinal study of persons aged 80 years or older (n = 346). An adjusted linear regression model was subsequently performed to calculate the regression coefficients of the associations between baseline physical and functional measures (dependent variable) with CZr or “Cu and Zn” alone taking also into account the influence of other relevant factors, including hematological (albumin, cholesterol, and urea) and inflammatory biomarkers (IL-6 and CRP) that were significantly different across CZr tertiles. CZr showed significant and stronger relationships than Cu or Zn alone with all baseline physical and functional measures in models that did not include adjustments for inflammatory parameters. CZr was also associated with physical decline, measured as “SPPB% decline” at 2 years of follow-up and mortality at 4 years of follow-up. Subjects in the high CZr tertile had a higher risk of death with an adjusted hazard ratio of 1.92 (95% CI, 1.12–3.29; p = 0.02). In conclusion, we have confirmed the role of CZr as a predictor of mortality, whereas the role of CZr as a biomarker or predictor of physical or functional performance seems to be the consequence of its strict relationships with inflammatory parameters. In this context, further investigations need to be carried out.

The prevalence of type 2 diabetes is increasing continuously, especially in older people. Such a rapidly rising risk has been linked to physical inactivity and evolutionary changes in dietary patterns (mainly characterized by a greater intake in dietary fat). Increased physical activity in any age group is associated with a lower risk of developing type 2 diabetes. Epidemiological studies also reported a lower incidence of type 2 diabetes in individuals who consumed n-3 polyunsaturated fatty acids (PUFA), while intake of total, saturated and/or monounsaturated fat was associated with increased risk of type 2 diabetes in glucose-intolerant individuals. Furthermore, the beneficial effects of PUFA consumption on cardiovascular disease were mainly attributed to their effects on reducing triglyceride levels, increasing high density lipoprotein cholesterol, and improving endothelial function through anti-inflammatory mechanisms and reduced platelet aggregation. In addition to common diabetic complications such as dyslipidemia and cardiovascular disease, elderly people with type 2 diabetes are at greater risk of specific geriatric syndromes, such as cognitive decline and physical disability. The threats of physical disability, loss of independence and loss of cognitive performance which diminish quality of life may ultimately be the greatest concern for those with type 2 diabetes. In this review we will address: i) specific dietary fat intake patterns and the development of insulin resistance and type 2 diabetes, ii) the effects of PUFA supplementation on glucose metabolism, diabetic dyslipidemia and cardiovascular disease, iii) the potential advantages of PUFA supplementation on cognitive decline and physical disability in the elderly.

Aging, oxidative stress and insulin resistance are strongly correlated. There is a growing body of evidence showing that aging is associated with a significant rise in oxidative stress mainly due to a decline in anti-oxidant activity and a rise in pro-oxidant factors such as glucose and insulin concentrations. Furthermore, aging is also associated with a progressive rise in insulin resistance which is due to a complex network of environmental, anthropometric and neuro-hormonal factors. It is noteworthy that extreme longevity, e.g. centenarians, is associated with a low degree of oxidative stress and insulin resistance. The causes for such differences between aged subjects and centenarians is not fully understood. It is likely that a specific genetic background might play a role. However, the insulin gene does not seem to be involved for explaining such age-related differences.

Aims To investigate the validity and reliability of the Audit of Diabetes-Dependent Quality of Life instrument in older Italians with diabetes and to test the association of diabetes-related quality of life with glycaemic control over time. Methods A total of 558 outpatients with Type 2 diabetes from the Diabetic Unit of the Italian National Research Centre on Aging Hospital in Ancona were enrolled to complete questionnaires (Audit of Diabetes-Dependent Quality of Life-19 and the Short-Form-12), and to undergo clinical and biochemical testing at baseline and at 12 months of follow-up. The overall impact of diabetes using the average weighted impact score from the Audit of Diabetes-Dependent Quality of Life questionnaire was calculated. Participants were categorized according to this score as having either less or more negative diabetes-related quality of life. Results Participants had a mean ± sd age of 67.7 ± 9.2 years and 51.8% were male. Factor analysis and Cronbach's coefficient of internal consistency (Cronbach's α = 0.931) confirmed that the 19 domain-specific Audit of Diabetes-Dependent Quality of Life items could be combined into a single scale in this Italian population. The impact score correlated with the physical (r = 0.275; P

Factor structure analyses have revealed the presence of specific biological system markers in healthy humans and diseases. However, this type of approach in very old persons and in type 2 diabetes (T2DM) is lacking. A total sample of 2,137 Italians consisted of two groups: 1,604 healthy and 533 with T2DM. Age (years) was categorized as adults (≤65), old (66-85), oldest old (>85-98) and centenarians (≥99). Specific biomarkers of routine haematological and biochemical testing were tested across each age group. Exploratory factorial analysis (EFA) by principal component method with Varimax rotation was used to identify factors including related variables. Structural equation modelling (SEM) was applied to confirm factor solutions for each age group. EFA and SEM identified specific factor structures according to age in both groups. An age-associated reduction of factor structure was observed from adults to oldest old in the healthy group (explained variance 60.4% vs 50.3%) and from adults to old in the T2DM group (explained variance 57.4% vs 44.2%). Centenarians showed three-factor structure similar to those of adults (explained variance 58.4%). The inflammatory component became the major factor in old group and was the first one in T2DM. SEM analysis in healthy subjects suggested that the glucose levels had an important role in the oldest old. Factorial structure change during healthy ageing was associated with a decrease in complexity but showed an increase in variability and inflammation. Structural relationship changes observed in healthy subjects appeared earlier in diabetic patients and later in centenarians.

We tested here the impact of a long-term inhibition of dipeptidyl peptidase-4 (DPP-4) with sitagliptin on the deposition of amyloid-beta within the brain and deficits in memory-related behavioral paradigms in a model of Alzheimer's disease (AD): double transgenic mice B6*Cg-Tg(APPswe,PSEN1dE9)85Dbo/J. Mice began to receive sitagliptin at 7 months of age. Three different dose of sitagliptin (5, 10 and 20 mg/kg), were administered daily for 12 weeks by gastric gavage. The treatments counteracted: (i) the memory impairment in the contextual fear conditioning test; (ii) increased the brain levels of GLP-1; (iii) produced significant reductions of nitrosative stress and inflammation hallmarks within the brain, as well as (iv) a significant diminution in the ultimate number and total area of betaAPP and Abeta deposits. All these effects much more evident for the dose of 20 mg/kg sitagliptin. The long-term inhibition of the endogenous DPP-4 enzymes with sitagliptin can significantly delay some forms of AD pathology, including amyloid deposition, when administered early in the disease course of a transgenic mouse model of AD.

Due to supporting evidence that dietary patterns may have a significant role in the maintenance of good physical performance with aging, we tested whether plasma fatty acids, saturated fatty acids (SFA), and polyunsaturated (PUFA) fatty acids are cross-sectionally associated with different physical performance and predict changes in physical performance over a 3-year period. Data were from the InCHIANTI study, a population-based study of older Italians. Plasma fatty acids were measured at enrollment (1998-2000), and outcome variables, Summary Physical Performance Battery (SPPB), and time to walk 7 meters (m) were measured at enrollment and after 3 years (2001-2004). At enrollment, 330 participants had significantly impaired lower extremity performance (defined as a SPPB score < or = 9). Adjusting for age, participants with a SPPB score > 9 had higher levels of total PUFA, n-3 PUFA, and n-6 PUFA, while significantly lower levels of SFA than those with a SPPB score < 9. Baseline SPPB scores were also associated with n-3 PUFA (beta = 0.148, p = 0.031), whereas the 7-m walk time was associated with total PUFA (beta = - 0.068, p = 0.008), after adjusting for potential confounders. Of the 884 participants with a SPPB score > 9 at baseline, 114 (12.9%) developed impaired lower extremity performance (SPPB < or = 9). In fully adjusted logistic models, baseline n-3 PUFA levels were inversely related to the risk of developing a decline in SPPB to < or = 9 (odds ratio [OR] = 0.21; 95% confidence interval [CI] = 0.08-0.53), while the n-6/n-3 ratio was associated with a higher risk of SPPB decline to < or = 9 (OR = 5.23; 95% CI = 2.02-13.51). In multivariate regression models, the n-6/n-3 ratio was associated with a longer time to walk 7 m (beta = 0.396, p = 0.037). n-3 PUFA plasma levels, which most likely reflect dietary intake, seem to protect against accelerated decline of physical performance. A higher n-6/n-3 ratio was associated with higher risk of developing poor physical performance and slower walking speed.

Life expectancy has significantly increased over the past 30 years, with a greater prevalence of diverse disease states, especially type 2 diabetes mellitus. As older persons are a very heterogeneous group with an increased prevalence of comorbidities and a relative inability to tolerate the adverse effects of oral antidiabetic agents, the treatment of type 2 diabetes is particularly demanding. The principles of its management are similar to those in younger patients, but with special considerations linked to comorbidities and clinical status. The available oral antidiabetic drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), alpha-glucosidase inhibitors, thiazolidinediones and newly introduced inhibitors of glucagon-like peptide 1 degrading enzyme dipeptidyl peptidase 4 (DPP-4). In addition, clinical aspects complicate diabetes care in the elderly, including cognitive disorders, physical disability and geriatric syndromes, such as frailty. The European Diabetes Working Party for Older Persons has increased glycaemic recommendations for target haemoglobin A(1c) from

Background. Cognitive decline that occurs frequently in impaired glucose tolerance (IGT) may be largely due to endothelial dysfunction. We assessed: (i) the relationships between impact of urinary albumin excretion rate (UAER), as marker of generalized endothelial dysfunction, and cognition; (ii) if cognitive decline could be explained by arterial stiffening using pulse wave velocity (PWV). Methods. One hundred forty older patients (age range 70‐85 years) with IGT and no dementia were selected. Patients were classified according to 24-hour UAER: normoalbuminuric (NA) (UAER , 20 lg/min) or microalbuminuric (MA) (UAER between 20 and 199 lg/min). Cognitive abilities were assessed by the Mini-Mental State Examination (MMSE) and a composite score of executive and attention functioning (CCS) at baseline and after 12 months of follow-up. Results. In MA patients (n ¼ 80), increased UAERs correlated with intimal media thickness (IMT) (r ¼ 0.268; p ¼ .02) and PWV (r ¼ 0.310; p ¼ .004). In the same group, increased UAERs were correlated with MMSE and CCS even after adjusting for age and mean arterial blood pressure (MABP). After adding PWV, the associations among UAERs, MMSE, and CCS were no longer significant. In MA patients, PWV correlated with IMT, MMSE, and CCS. In NA patients, no significant correlations were found among UAERs, MMSE, and CCS. At follow-up, baseline UAERs predicted an approximately 20% risk of poor cognition (according to MMSE and CCS) after adjusting for confounders. After adding PWV, UAERs no longer predicted cognitive performance. Conclusions. MA older persons with IGT showed a decline in cognition performance that may be partially explained by arterial stiffness.

The increasing proportion of elderly persons in the global population, and the implications of this trend in terms of increasing rates of chronic diseases such as type 2 diabetes mellitus, continue to be a cause for concern for clinicians and healthcare policy makers. The diagnosis and treatment of type 2 diabetes in the elderly is challenging, as age-related changes alter the clinical presentation of diabetic symptoms. Once type 2 diabetes is diagnosed, the principles of its management are similar to those in younger patients, but with special considerations linked to the increased prevalence of co-morbidities and relative inability to tolerate the adverse effects of medication and hypoglycaemia. In addition, there are many underappreciated factors complicating diabetes care in the elderly, including cognitive disorders, physical disability and geriatric syndromes, such as frailty, urinary incontinence and pain. Available oral antihyperglycaemic drugs include insulin secretagogues (meglitinides and sulfonylureas), biguanides (metformin), alpha-glucosidase inhibitors and thiazolidinediones. Unfortunately, as type 2 diabetes progresses in older persons, polypharmacy intensification is required to achieve adequate glycaemic control with the attendant increased risk of adverse effects as a result of age-related changes in drug metabolism. The recent introduction of the incretins, a group of intestinal peptides that enhance insulin secretion after ingestion of food, as novel oral antihyperglycaemic treatments may prove significant in older persons. The two main categories of incretin therapy currently available are: glucagon-like peptide-1 (GLP-1) analogues and inhibitors of GLP-1 degrading enzyme dipeptidyl peptidase-4 (DPP-4). The present review discusses the effect of aging on metabolic control in elderly patients with type 2 diabetes, the current treatments used to treat this population and some of the more recent advances in the field of geriatric type 2 diabetes. In particular, we highlight the efficacy and safety of GLP-1 and DPP-4 inhibitors, administered as monotherapy or in combination with other oral antihyperglycaemic agents, especially when the relevant clinical trials included older persons. There is strong evidence that use of incretin therapy, in particular, the DPP-4 inhibitors, could offer significant advantages in older persons. Clinical evidence suggests that the DPP-4 inhibitors vildagliptin and sitagliptin are particularly suitable for frail and debilitated elderly patients because of their excellent tolerability profiles. Importantly, these agents lack the gastrointestinal effects seen with metformin and alpha-glucosidase inhibitors taken alone, and have a low risk of the hypoglycaemic events commonly seen with agents that directly lower blood glucose levels.

In the April, 2007, issue of the Archives, Barzilay et al1 reported that 2 components of the metabolic syndrome, insulin resistance (IR) and inflammation, are associated with the risk of frailty in older persons without diabetes mellitus, severe cognitive impairment, or other chronic illnesses. Using the homeostasis model of assessment (HOMA), they found that IR and C-reactive protein were consistently associated with an increased risk of developing frailty, even after adjusting for confounders. The authors propose that there is a causative relationship between IR and frailty. Specifically, they propose that the progressive age-associated decline of insulin sensitivity causes an imbalance toward catabolism, which is clinically expressed as an accelerated decline of muscle mass and strength. Such findings further substantiate previous findings from the “Invecchiare in Chianti” (InCHIANTI) study showing that IR-HOMA score was independently associated with poor muscle strength in older persons.2 Barzilay et al1 also hypothesized the existence of an inflammatory IR pathway that could contribute to muscle weakness and poor physical performance. An independent cross-sectional relationship between inflammatory markers and IR-HOMA score was previously suggested from analyses performed in the InCHIANTI database that underlined significant associations among IR and diverse inflammatory cytokines.3 Interestingly, Barzilay et al1 did not consider cognitive decline as part of their outcome. Indeed, cognitive impairment is often observed in frail older persons, and several authors have proposed that cognitive impairment should be an essential component of the frailty definition.4 There is strong evidence showing that normal functioning of the insulin-signaling pathway is crucial for the maintenance of adequate cognitive function.5 We studied the relationship between IR-HOMA score and global cognitive performance (Mini-Mental State Examination [MMSE]) as well as executive functioning (Trail-Making Test [TMT] times) in 597 older persons with a mean age of 73 years from the InCHIANTI study.5 After adjusting for multiple confounders including MMSE score, IR-HOMA score was significantly associated with poor visual scanning (TMT-A) (β=11.005; P=.02), poor visual scanning with added cognitive flexibility (TMT-B) (β=28.379; P

Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women (≥65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone ( P < 0.001), IL-6 ( P < 0.001), CRP ( P < 0.001), and HOMA ( P < 0.001) and lower levels of SHBG ( P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of MetS ( P < 0.0001) vs. those with low SHBG. In a further model including all hormones and confounders, log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI 0.21–0.91, P = 0.027). In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance. Further studies are needed to support the notion that raising SHBG is a potential therapeutic target for prevention and treatment of MetS.

OBJECTIVE—Several studies have demonstrated that endothelial dysfunction plays a central role in diabetic mortality and that the prooxidative effect of postprandial hyperglycemia may actively contribute to atherogenesis. Thus, we investigated the possible effect of short-acting (repaglinide) and long-acting (glibenclamide) insulin secretagogues on endothelial function in type 2 diabetic patients. RESEARCH DESIGN AND METHODS—Sixteen type 2 diabetic patients undergoing diet treatment and with poor glucose control volunteered for the study. The study was designed as a 4-month, randomized, cross-over, parallel-group trial of repaglinide (1 mg twice a day) versus glibenclamide (5 mg twice a day). All patients underwent the following investigations: 1) anthropometrics determinations, 2) blood sampling for routine laboratory analyses and for assessment of oxidative stress indexes, and 3) a brachial reactivity test to evaluate the endothelial function through the study of arterial diameter and flow changes with and without intraarterial infusion of NG-monomethyl-l-arginine, an inhibitor of nitric oxide synthase and tetraethylammonium chloride (TEA), a Ca2+-activated K+ (KCa) channel blocker. All patients were randomly assigned to receive repaglinide or glibenclamide for a period of 4 weeks. RESULTS—Repaglinide administration was associated with a significant reduction in 2-h plasma glucose levels (P < 0.001) and in plasma thiobarbituric acid–reactive substances (TBARS) concentrations (P < 0.001) and with a significant increase in plasma antioxidant power, assessed as Trolox equivalent antioxidant capacity (TEAC) (P < 0.001), effects not observed after glibenclamide administration. With regard to brachial reactivity parameters, repaglinide but not glibenclamide was associated with a significant improvement in brachial reactivity parameters (P < 0.003 for all parameters). In contrast, intra-arterial infusion ofl-NMMA and TEA reduced the beneficial effect of repaglinide. CONCLUSIONS—Repaglinide administration, through good control of postprandial glucose levels, improves brachial reactivity and declines oxidative stress indexes.

To test the association between cognitive impairment, with and without subcortical features, and insulin resistance in an elderly community-dwelling population.Cross-sectional wave of an epidemiologic longitudinal study (InCHIANTI).A total of 523 people, aged 70 to 90 years without diabetes mellitus or hyperglycemia, from the InCHIANTI cohort were included in the study. A total of 119 individuals had cognitive impairment (Mini-Mental State Examination [MMSE] score25), 21 of whom had both cognitive impairment and subcortical features (CI/SF+ group). Control groups contained 23 individuals with a history of stroke and 381 individuals with no cognitive impairment (no CI group, MMSE scoreor = 25). Indicators of insulin resistance were the fasting plasma insulin level, insulin resistance index (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and insulin sensitivity index (Quantitative Insulin Sensitivity Check Index [QUICKI]).The insulin resistance profile of patients in the CI/SF+ group was similar to that of individuals who had experienced stroke, whereas the profile of individuals with cognitive impairment without subcortical features (CI/SF- group) was similar to that of individuals in the no CI group. Patients in the CI/SF- group showed insulin resistance comparable to individuals in the no CI group (age-adjusted P = .27, .19, and .64, respectively, for difference in fasting blood insulin level, HOMA-IR, and QUICKI in linear regression models) and lower than patients with stroke (age-adjusted P = .01, .02, and .07, respectively). On the contrary, patients in the CI/SF+ group had insulin resistance and sensitivity values similar to those of the stroke group (age-adjusted P = .80, .84, and .75, respectively, for difference in fasting blood insulin level, HOMA-IR, and QUICKI) but significantly different from those in the no CI group (age-adjusted P = .01, .03, and .02, respectively).Cognitive impairment with but not without subcortical features is associated with biochemical and clinical features of insulin resistance syndrome. In epidemiologic populations, insulin resistance might contribute to cognitive impairment through a vascular mechanism.

Recent studies have demonstrated that C-peptide exerts beneficial effects on endothelial function. To investigate the relationship between residual pancreatic C-peptide secretion and endothelial function in patients with well controlled or poorly controlled Type II diabetes, we studied 100 patients with Type II diabetes that were free from diabetic neuropathy. In all patients, insulin resistance, residual pancreatic C-peptide secretion, endothelial function and oxidative stress were investigated using the homoeostasis model assessment (HOMA) index, glucagon bolus test, brachial reactivity, Trolox equivalent antioxidant capacity (TEAC) and thiobarbituric acid-reacting substances (TBARS). The patients were categorized into quartiles on the basis of plasma HbA 1c (glycated haemoglobin) concentration. Analysis of the data showed significant increases in plasma glucose concentration, HOMA index, microalbuminuria and TBARS, and significant decreases in plasma C-peptide, AUC (area under the curve) plasma C-peptide and TEAC, through the different quartiles (from the lowest to the highest HbA 1c concentration). With regard to parameters of endothelial function, changes in diameter showed a significant declining trend through the different quartiles. Endothelial-dependent changes in diameter were independently and significantly associated with AUC C-peptide levels, TEAC and TBARS. In conclusion, our study demonstrated that patients with Type II diabetes with good residual C-peptide secretion are better protected from endothelial dysfunction that those with poor C-peptide secretion.

Background. The functional consequences of an age-related insulin resistance (IR) state on muscle functioning are unknown. Because insulin is needed for adequate muscle function, an age-related insulin-resistant state may also be a determining factor. We evaluated the relationship between IR and handgrip muscle strength in men and women from a large population-based study (n ¼ 968). Methods. The degree of IR was evaluated by the homeostasis model assessment (HOMA) and muscle strength was assessed using handgrip. Results. Simple sex-stratified correlations demonstrated that, in men, body mass index-adjusted handgrip strength correlated positively with physical activity (r ¼0.321; p , .001), muscle area (r ¼0.420; p , .001), muscle density (r ¼ 0.263; p ¼ .001), plasma albumin (r ¼ 0.156; p ¼ .001), insulin-like growth factor-1 (r ¼ 0.258; p , .001), calcium (r ¼ 0.140; p ¼.006), and testosterone (r ¼0.325; p , .001) concentrations, whereas a negative association was found for age (r ¼� 0.659; p , .001) and myoglobin plasma levels (r ¼� 0.164; p ¼ .001). In women, body mass index-adjusted handgrip strength correlated positively with physical activity (r ¼ 0.280; p , .001), muscle area (r ¼ 0.306; p , .001), muscle density (r ¼ 0.341; p ¼ .001), plasma albumin (r ¼ 0.140; p ¼ .001), and insulin-like growth factor-1 (r ¼ 0.300; p , .001), whereas a negative association was found for age (r ¼� 0.563; p , .001), myoglobin levels (r ¼� 0.164; p ¼ .001), and IR (r ¼� 0.130; p ¼ .04). Conclusions. Sex-stratified analyses adjusted for multiple confounders showed that the relationship between IR and handgrip strength was found significant in women, whereas it was negligible and not significant in men.