The selective peroxisome proliferator-activated receptor alpha modulator (SPPARM) 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 (SPPARM) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARM 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 SPPARM agonist safely reduces residual cardiovascular risk.Peer reviewe

Residual vascular risk in diabetes – will the SPPARM alpha concept hold the key?

No abstract available

Le diabète en Belgique et dans le monde : quo vadis?

Le diabète sucré est un défi de santé sociétal à l’échelle universelle, devenu majeur. Deux raisons principales en rendent compte : son évolution épidémique et le risque de complications chroniques secondaires à l’hyperglycémie. Le but de cet article est de mieux mettre en évidence le problème du (pré)diabète en 2016 et de suggérer des approches qui permettraient de mieux contrôler la maladie (prédiabète et diabète) et ses conséquences.[Diabetes in Belgium and worldwide: quo vadis?] Diabetes Mellitus is a major health problem for at least two main reasons: the disease's epidemic evolution and the risk of chronic, hyperglycemia-related complications. This article aims at emphasizing the worldwide health problem of (pre)diabetes, while presenting approaches in order to better control the disease and its consequences

Here we go again ... the metabolic syndrome revisited!

Whilst all innovations and new ideas will have their passionate proponents, one of the sine qua non of the medical world is that it will also have its opponents. The concept of the metabolic syndrome was no exception and went through its debates and controversies. With the harmonization between the AHA/NHLBI and the IDF definitions for the diagnosis of the metabolic syndrome, one would have hoped that that we would now take a step forward and thrash out a consensus on the metabolic syndrome between the opponents and the proponents so that we could leave this controversy behind us. But a WHO Expert Consultation Group recently came out with a report which basically reiterated the old arguments, though in a more nuanced manner, which had been used by those opposing the concept of the metabolic syndrome from its initial stages. The report points out that, despite an exponential increase in the number of research papers on the subject, no single unifying pathophysiological mechanism has been agreed, and the equivalence of the risk factors and their cutoff points across different populations has not been established. The criteria used to diagnose the metabolic syndrome have major limitations including: the dichotomisation of risk factors; the attribution of relative as opposed to absolute risk; the differing predictive value of risk factor combinations; the inclusion of individuals with established diabetes and heart disease; and the omission of important risk factors for predicting diabetes and CVD. A formal diagnosis of the metabolic syndrome is rarely made in routine clinical practice, and the concept has not been widely adopted in national guidelines for the prediction of CVD or diabetes. The end recommendation was that whilst, it may be considered useful as an educational concept, it should be considered a premorbid condition with limited practical utility as a diagnostic or management tool. Many of these questions have been answered in the past. The need of the hour is not too guard one's turf or come out with controversial statements, which frankly are no more than hindrances at least in this instance, but accept that we are facing a major problem as far as the ravages associated with T2DM and ASCVD are concerned and that we have to join hands and take immediate and definitive steps to prevent and optimally manage the risk factors associated with these pandemics. This can only be done by empowering both patients, and especially the primary care givers, who in many instances are the first, and often, the only medical personnel who a person has access to. Highly academic guidelines dictated by a few people are not the way forward. We need to be inclusive, take ground realities into consideration to help various regions and countries evolve the most optimal way forward. It would be better for the WHO consultation group to accept that, with the metabolic syndrome, we have a tool in our hands which can make both the treating physicians as well as the people aware of the need for early diagnosis and a comprehensive treatment of any, and all, risk factors for T2DM and ASCVD, and which would be "available, accessible and affordable" to most, if not all, people, rather than discard this as being "a premorbid condition of no clinical utility but just an exercise in futility". © 2009 Diabetes India. Published by Elsevier Ltd. All rights reserved

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

High rates of atherogenic dyslipidemia, β-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). β-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 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 patient

Size, density and cholesterol load of HDL predict microangiopathy, coronary artery disease and β-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, β-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 β-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

Type 1 diabetes registry in developing countries: Perspective from India

India has been a prey to rising tide of non-communicable diseases. It is becoming increasingly important to evolve strategies to ensure effective prevention, diagnosis and treatment of this rising burden. Available Indian data reveal different opinions regarding type 1 diabetes (T1D). Such variation in data leads to uncertainty in healthcare planning and management. This ununiformity in data and the absence of protocol make a task challenging. Many patients consult non-specialists and even doctors from different streams. On the part of the patients, the diagnostic and screening testing are a great burden. T1D registry is of great relevance to India. It helps in ensuring good clinical practice and errors. Endocrinologists and paediatricians can audit themselves using such a registry. The overall goal is to improve population health. The objective is to reduce morbidity and mortality while maximising the cost-effectiveness. Such a registry helps in fund allocation and healthcare planning and contributes to the formulation of pragmatic management guidelines. However, healthcare professionals are reluctant to share their data. This may be due to fear of being audited by peers or regulators and record maintenance. We must work towards creating a national registry of T1D. This should involve multiple centres across the country, as it will help enhance awareness about T1D and improve standard of care. The results of which can be used to advocate for greater allocation of resources to T1D care. An effective registry will help children claim their rightful place under the sun