Established and novel gender dimorphisms in type 2 diabetes mellitus: Insights from a multiethnic cohort.

BACKGROUND AND AIMS: In type 2 diabetes mellitus (T2DM), sexual dimorphisms modulate the natural histories of hyperglycemia, anthropophysical/cardiometabolic phenotype, and susceptibility to chronic micro and macrovascular complications. The purpose of this work was to revisit known or new dimorphisms within a multiethnic cohort. METHODS: Among 1238 T2DM patients, men (63%) were compared to women (37%), including leading ethnicities: Whites (67.4%; 542 men; 293 women); Maghrebians (9.4%; 62 men; 54 women); and Blacks (12.5%; 92 men; 63 women). RESULTS: Age, BMI, diabetes duration, insulin sensitivity, B-cell function loss, HbA1c, and hyperglycemia index were similar in both genders. All-cause microangiopathy and cerebrovascular disease did not differ between sexes. Women had significantly more retinopathy (27% vs. 21%) and men more microalbuminuria (25% vs. 19%), all-cause macroangiopathy (40% vs. 26%), CAD (29% vs. 17%) and PAD (11% vs. 6%). Among Blacks, sexual dimorphism in terms of retinopathy was more pronounced (24% in women vs. 11%), while there was no sexual dimorphism in all-cause macroangiopathy, CAD or PAD. B-cell function loss was faster among North African men (+15%), who also had more hepatic steatosis (+27%) than women. CONCLUSIONS: T2DM abolishes the CV protection provided by the female gender in Blacks. In White women, the loss of CV protection in diabetes is limited to cerebrovascular disease. In Black women, a markedly increased risk of retinopathy is present, despite glycemic exposure similat to men. Sexual dimorphisms do not affect glucose homeostasis and metabolic control in all ethnicities, except for lesser B-cell function loss in Maghrebian women.

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation.

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

Strengthening the Family - the 'Five-I' Approach.

This article describes the importance of the family in diabetes care. It lists the multiple ways in which the family is related to diabetes: as a cause or culprit of diabetes, as a tool or technique for delivering diabetes care and as a target of diabetes or diabetes-care-related complications. The authors suggest an alliterative 'Five-I' approach to guide diabetes care professionals in addressing needs, and utilising strengths, of the family of a person with diabetes. The five 'I's stand for: involved independence, iterative information, interactive interviews, inspired introspection and integrated incorporation. This strategy, based upon evidence and experience, is supported by pragmatism and practicality.

Recommendations for in-clinic PoCT for diabetes management in India.

A panel of expert diabetologist clinicians developed consensus standards to address the quality gaps inclinic point of care testing (PoCT) especially pertaining to diabetes care and management in India. The following summarized principles were established- 1. PoCT definition, 2. Advantages and critical aspects of PoCT including guideline recommendations and accreditations, analytical factors (pre &post analytical included) and consensus reached for an ideal PoC analyzer and 3. Key recommendations on in-clinic PoCT implementation by the panel. The experts suggested next steps that included key comparative (PoCT vs NGSP accredited lab) and patient benefit studies on PoCT.

High rates of atherogenic dyslipidemia, ß-cell function loss, and microangiopathy among Turkish migrants with T2DM.

AIMS: Non-Caucasian migrants require dedicated approaches in diabetes management due to specific genetic; socio-cultural; demographic and anthropological determinants. Documenting such phenotypes allows for better understanding unmet needs and management priorities. METHODS: This age- and sex-adjusted case-control (1:6 ratio) study compared 56 T2DM Turkish migrants (70% males) resident in Belgium [Tu] with 336 T2DM Caucasians [Ca], all benefiting from state-funded healthcare. RESULTS: The 2 groups did not differ regarding BMI; waist circumference; fat mass; visceral fat; muscle mass; insulin sensitivity; insulinemia; metabolic syndrome; hypertension; lipid-modifying drugs; and macroangiopathy. They also had similar renal function and (micro)albuminuria. Education (low/high) and ethanol consumption were lower among [Tu]: 83/17% and 2.0 U/wk vs 43/57% and 13.6 U/wk in [Ca] (p < 0.0001). ß-cell function loss (BCF) was higher in [Tu]: 1.58(0.45) vs 1.35(0.54)%/yr (p 0.0027), as was HbA1c: 8.39(1.91) vs 7.48(1.35)% in [Ca] (p < 0.0001). Diabetes duration and insulin use were increased in [Tu]: 19(9)yr and 70% vs 16(8)yr and 48% in [Ca] (p 0.0111 and 0.0024). Atherogenic dyslipidemia (AD) was more prevalent in [Tu]: 64% vs 49% (p 0.0309), who had higher non-HDL-C; apolipoprotein B100; LDL-C; and triglycerides; and lower HDL-C and apolipoprotein A-I levels (all p < 0.05). Overall microangiopathy; retinopathy; and neuropathy were more prevalent in [Tu]: 55-35-37% vs 40-18-20% in [Ca] (all p < 0.05). CONCLUSIONS: These results should raise concerns about poor glycaemic control; rapid BCF loss; severe AD; and microangiopathy among Turkish migrants with T2DM. Targeting AD could improve the cardiometabolic profile of this minority given the relationship between AD and residual vascular risk.

The Berlin Declaration: A call to improve early actions related to type 2 diabetes. Why is primary care important?

Diabetes is epidemic worldwide and places a huge burden on healthcare systems. The majority of the cost of type 2 diabetes (T2D) is related to hospitalization and the management of complications, and these also have a negative impact on the individual's quality of life. The Berlin Declaration is a global call for early action for the identification of high risk individuals, prevention of T2D and the prevention of complications in those with T2D, through prevention, early detection, early control and early access to the right multidisciplinary interventions. This should empower people to take action to prevent T2D and its complications.

The Berlin Declaration: A call to action to improve early actions related to type 2 diabetes. How can specialist care help?

Diabetes is a major global epidemic and places a huge burden on healthcare systems worldwide. The complications of type 2 diabetes (T2D) and related hospitalizations are major contributors to this burden, and there is strong evidence that the risk for these can be reduced by early action to identify and prevent progression of people at high risk of T2D and ensure tight glycemic control in those with established disease. In response to this, the Berlin Declaration was developed by four working groups of experts and ratified by healthcare professionals from 38 countries. Its aim is to act as a global call to action for early intervention in diabetes, in addition to providing short-, medium- and long-term targets that should be relevant to all nations. The Berlin Declaration focuses on four aspects of early action, and proposes actionable policies relating to each aspect: early detection, prevention, early control and early access to the right interventions. In addition, a number of treatment targets are proposed to provide goals for these policies. To ensure that the suggested policies are enacted in the most effective manner, the support of specialist care professionals is considered essential.

Clinical practice points for diabetes management during RAMADAN fast.

Diabetes management during Ramadan is very crucial from the patient perspective as it can present significant risk of hypoglycemia and death when proper care is not taken. Moreover, managing diabetes in fasting Ramadan patients require different mechanisms than the routine diabetes management and pose significant challenge to the health care practitioners. Here we set forth to review the available literature of various clinical trials and studies on different antidiabetic agents in the context of Ramadan. On the basis of available evidence, we suggest that gliclazide is effective and it could be safely recommended in type 2 diabetic patients fasting during Ramadan.

Evidence-based recommendations for insulin intensification strategies after basal insulin in type 2 diabetes.

Over the time due to progressive nature of diabetes, proactive intensification of the existing insulin therapy becomes imminent as it minimizes patients' exposure to chronic hypo/hyperglycaemia and reduces weight gain while achieving individualized glycaemic targets. This review focuses on the strength of evidence behind various options for intensification, primarily the insulins as also the GLP-1 analogues. The recommendations presented here are meant to serve as a guide for the physician managing type 2 diabetes patients requiring insulin intensification upon failing of basal insulin therapy.

Consensus recommendations on exploring effective solutions for the rising cost of diabetes.

Diabetes remains asymptomatic for a long period of time and its real burden gets noticed only once the complications set in. The number of individuals affected with the disease is also on the rise and more so in the low income countries. This scenario calls for urgent precautionary measures that need to be undertaken to equip ourselves to fight against this chronic disease. Individuals with financial constraints cannot afford to access even the basic treatment facilities and thus stands the most burdened. The International Diabetes Federation calls for 'Eyes on Diabetes' for the society to focus on early screening and early intervention. The rising cost of diabetes results from delayed and denied treatment. The panel discussion organized as a part of 4th Annual global diabetes convention of Jothydev's Professional Education Forum (JPEF, 2016) facilitated a platform to address diabetes as a serious health concern that needs to be given immediate priority by the policymakers as well as public and also to discuss about the feasible measures that will help achieve cost effective and affordable diabetes treatment. This was followed by in-depth literature search and finally a set of recommendations have been arrived at by the key opinion leaders to realize the dream of affordable diabetes care to all deserving individuals.

Size, density and cholesterol load of HDL predict microangiopathy, coronary artery disease and ß-cell function in men with T2DM.

The role of high-density lipoprotein cholesterol (HDL-C) as modifiable risk factor for cardiovascular (CV) disease is increasingly debated, notwithstanding the finding that small-dense and dysfunctional HDL are associated with the metabolic syndrome and T2DM. In order to better clarify the epidemiological risk related to HDL of different size/density, without resorting to direct measures, it would seem appropriate to adjust HDL-C to the level of its main apolipoprotein (apoA-I), thereby providing an [HDL-C/apoA-I] ratio. The latter allows not only to estimate an average size for HDLs, but also to derive indices on particle number, cholesterol load, and density. So far, the potential usefulness of this ratio in diabetes is barely addressed. To this end, we sorted 488 male patients with T2DM according to [HDL-C/apoA-I] quartiles (Q), to determine how the ratio relates to cardiometabolic risk, ß-cell function, glycaemic control, and micro- and macrovascular complications. Five lipid parameters were derived from the combined determination of HDL-C and apoA-I, namely HDL size; particle number; cholesterol load/particle; apoA-I/particle; and particle density. An unfavorable cardiometabolic profile characterized patients from QI and QII, in which HDLs were pro-atherogenic, denser and apoA-I-depleted. By contrast, QIII patients had an [HDL-C/apoA-I] ratio close to that of non-diabetic controls. QIV patients had better than average HDL size and composition, and in those patients whose [HDL-C/apoA-I] ratio was above normal, a more favorable phenotype was observed regarding lifestyle, anthropometry, metabolic comorbidities, insulin sensitivity, MetS score/severity, glycaemic control, and target-organ damage pregalence in small or large vessels. In conclusion, [HDL-C/apoA-I] and the resulting indices of HDL composition and functionality predict macrovascular risk and ß-cell function decline, as well as overall microangiopathic risk, suggesting that this ratio could serve both in cardiometabolic assessment and as biomarker of vascular complications.

Unproven Therapies for Diabetes and Their Implications.

Diabetes is a chronic disease and is one of the leading causes of morbidity and mortality worldwide. Being an ancient disease, many individuals follow complementary and alternative medicinal (CAM) therapies for either the cure or prevention of the disease. The popularity of these practices among the general public is in no way a testimony to their safety and efficacy. Due to the possibility of undesirable interactions with conventional medicines, it is imperative that patients are asked about CAM use during patient assessment. Patient- and physician-targeted awareness programs on various aspects of CAM use must be initiated to create a better understanding of evidence-based use of these practices. In addition, there should be guidelines in place based on clinical trial outcomes, and stricter regulations need to be enforced on CAM practices to ensure their safety and effectiveness.

Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: a Joint Statement by International Diabetes Organizations.

BACKGROUND: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options. AIM: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D. METHODS: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005-30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28-30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee. RESULTS: Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI ≥40 kg/m2) and in those with class II obesity (BMI 35.0-39.9 kg/m2) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0-34.9 kg/m2 if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m2 for Asian patients. CONCLUSIONS: Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies.

Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations.

BACKGROUND: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options. AIM: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D. METHODS: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005-30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28-30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee. RESULTS: Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI≥40 kg/m(2)) and in those with class II obesity (BMI 35.0-39.9 kg/m(2)) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0-34.9 kg/m(2) if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m(2) for Asian patients. CONCLUSIONS: Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies.

Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations.

BACKGROUND: Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options. AIM: The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D. METHODS: A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005-30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28-30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee. RESULTS: Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI ≥40 kg/m(2)) and in those with class II obesity (BMI 35.0-39.9 kg/m(2)) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0-34.9 kg/m(2) if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m(2) for Asian patients. CONCLUSIONS: Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies.

The normal-weight type 2 diabetes phenotype revisited.

BACKGROUND: Type 2 diabetes (T2DM) is associated with obesity, insulin resistance and the metabolic syndrome (MetS). In non-diabetic populations, features of metabolic obesity (MO) are observed in a minority of normal-weight (NW) subjects. The cardiometabolic status of metabolically obese but normal-weight (MONW) individuals has not yet been phenotyped in T2DM. PATIENTS AND METHODS: Prevalence and features of MONW were analyzed in 1244 T2DM patients, in whom MONW was identified as a BMI <25.0 and a MetS score ≥3/5. Among NW (n=262; 21%), those without MetS (n=152; NW-MetS[-]) were compared to NW-MetS[+] (n=110; i.e. 42% of NW and 9% of all T2DM). RESULTS: There were no differences between groups in age; gender; diabetes duration; smoking; BP; and LDL-C. NW-MetS[+] had higher BMI; waist; fat mass; visceral fat; liver steatosis and HbA1c, and lower insulin sensitivity. Non-right-handedness was twice-higher (18%) in NW-MetS[-]. NW-MetS[+] had higher apoB100 and triglycerides, and lower HDL-C and LDL size. Macroangiopathy was present in 39% of NW-MetS[+] vs. 22% of NW-MetS[-], as coronary (23% vs. 14%) or peripheral artery disease (14% vs. 5%) and TIA/stroke (15% vs. 7%). Microangiopathy was present in 54% of NW-MetS[+] vs. 32% of NW-MetS[-], as retinopathy (25% vs. 13%); neuropathy (29% vs. 18%); and albuminuria (39% vs. 20%). CONCLUSIONS: MONW among T2DM represents a significant minority (about 1 in 10). Their cardiometabolic phenotype deserves attention due to multiple comorbidities, including a twice-higher prevalence of micro-/macrovascular damage in patients wrongly perceived at lower risk due to normal BMI. Unexpectedly, non-right-handedness was over-represented among metabolically healthy patients.

Consensus Statement on Management of Post-Prandial Hyperglycemia in Clinical Practice in India.

Postprandial hyperglycemia (PPHG) is a detrimental factor in the evolution of diabetes related complications. Numerous studies have established the role of PPHG in development of atherosclerosis and associated cardiovascular conditions. It is seen that management of PPHG can be more troublesome than fasting plasma glucose (FPG). Currently, there are various strategies both monitoring as well as therapeutic to control PPHG but there is no uniformity in practicing these strategies. In the absence of any standard guidelines, widespread variations in the management of PPHG are observed among physicians and diabetologists. The objective of this document is to set forth uniform guidelines to manage PPHG. This will not only result in optimal management and prevention of long term complications of diabetes but also better co-ordination and collaboration among the care providers. Moreover, an Indian perspective that can take into consideration the issues relevant to Indian patient pool will be effective. An expert committee comprising of prominent physicians and researchers associated with diabetes care provided their inputs to provide a basic platform for the formulations of guidelines. Their inputs were supplemented by extensive literature search to collect the relevant evidences. An initial draft was prepared which was reviewed by the core committee. Inputs from other experts were also sought and an initial guideline version was formulated that was presented in a conference, discussed and debated among experts. The guidelines on PPHG were then finalized and published.

Challenges in Type 1 diabetes management in South East Asia: Descriptive situational assessment.

Treatment of type 1 diabetes is a challenging issue in South East Asia. Unlike in the developed countries, patients have to procure insulin, glucometer strips and other treatment facilities from their own pockets. Coupled with poor resources are the difficulties with diagnosis, insulin initiation, insulin storage, marital and emotional challenges. Being a disease affecting only a minority of people, it is largely ignored by the governments and policy makers. Comprehensive diagnostic, treatment and team based educational facilities are available only in the speciality diabetes centers in the private sector whereas majority of the subjects with type 1 diabetes are from a poor socio-economic background. Unlike in the Western world, being known as a diabetes patient is a social sigma and poses huge emotional burden living with the disease and getting married. Even with best of the resources, long-term treatment of type 1 diabetes still remains a huge challenge across the globe. In this review, authors from India, Pakistan, Nepal, Sri Lanka, Myanmar and Bangladesh detail the country-specific challenges and discuss the possible solutions.