Insulin secretion in metabolically obese, but normal weight, and in metabolically healthy but obese individuals

Metabolically obese but normal-weight (MONW) individuals present metabolic disturbances typical of obese individuals. Additionally, metabolically healthy but obese (MHO) individuals have been identified who are relatively insulin sensitive and have a favorable cardiovascular risk profile. We compared insulin secretion patterns of MONW and MHO with those of two age-matched groups comprising nonobese individuals or obese insulin-resistant subjects, respectively. To this end, 110 nonobese subjects and 87 obese subjects were stratified into quartile based on their insulin-stimulated glucose disposal (M(FFM)). Insulin secretion was estimated by acute insulin response (AIR) during an intravenous glucose-tolerance test (IVGTT), and the disposition index was calculated as AIR x M(FFM). We found that, as defined, M(FFM) was lower in MONW, who exhibited higher triglycerides, free-fatty acid (FFA), and 2-h postchallenge glucose levels compared to normal nonobese group. Insulin secretion was higher in MONW than in normal nonobese subjects, but disposition index was lower in MONW. Disposition index did not differ between MONW and insulin-resistant obese. M(FFM) was higher in MHO who exhibited lower waist circumference, blood pressure (BP), triglycerides, FFA, insulin levels, and higher high-density lipoprotein (HDL) cholesterol compared to insulin-resistant obese. Insulin secretion did not differ between insulin-resistant obese and MHO, but disposition index was lower in the former group. In conclusion, MONW and insulin-resistant obese showed decreased compensatory insulin secretion compared to normal nonobese and MHO subjects, respectively. Because these subjects also exhibited a worse metabolic risk profile, these findings may account for their increased risk for type 2 diabetes.     

Metabolically healthy obesity and metabolically obese normal weight: a review

Journal of Physiology and Biochemistry - Despite the general relationship between obesity and its co-morbidities, there are both obese individuals who scarcely present the associated pathologies...     

Diet composition and activity level of at risk and metabolically healthy obese american adults

Objective:

Obesity often clusters with other major cardiovascular disease risk factors, yet a subset of the obese appears to be protected from these risks. Two obesity phenotypes are described, (i) “metabolically healthy” obese, broadly defined as body mass index (BMI) ≥ 30 kg/m² and favorable levels of blood pressure, lipids, and glucose; and (ii) “at risk” obese, BMI ≥ 30 with unfavorable levels of these risk factors. More than 30% of obese American adults are metabolically healthy. Diet and activity determinants of obesity phenotypes are unclear. We hypothesized that metabolically healthy obese have more favorable behavioral factors, including less adverse diet composition and higher activity levels than at risk obese in the multi‐ethnic group of 775 obese American adults ages 40‐59 years from the International Population Study on Macro/Micronutrients and Blood Pressure (INTERMAP) cohort.

Design and Methods:

In gender‐stratified analyses, mean values for diet composition and activity behavior variables, adjusted for age, race, and education, were compared between metabolically healthy and at risk obese.

Results:

Nearly one in five (149/775 or 19%) of obese American INTERMAP participants were classified as metabolically healthy obese. Diet composition and most activity behaviors were similar between obesity phenotypes, although metabolically healthy obese women reported higher sleep duration than at risk obese women.

Conclusions:

These results do not support hypotheses that diet composition and/or physical activity account for the absence of cardiometabolic abnormalities in metabolically healthy obese.     

Effects of weight loss in metabolically healthy obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet

Weight loss in metabolically healthy obese (MHO) subjects may result in deterioration of cardio-metabolic risk profile. We analyzed the effects of weight loss induced by laparoscopic adjustable gastric banding (LAGB) on cardio-metabolic risk factors in MHO and insulin resistant obese (IRO) individuals. This study included 190 morbidly obese non-diabetic subjects. Obese individuals were stratified on the basis of their insulin sensitivity index (ISI), estimated from an OGTT, into MHO (ISI index in the upper quartile) and IRO (ISI in the three lower quartiles). Anthropometric and cardio-metabolic variables were measured at baseline and 6-months after LAGB. Six months after LAGB, anthropometric measures were significantly reduced in both MHO and IRO. Percent changes in body weight, BMI, and waist circumference did not differ between the two groups. Fasting glucose and insulin levels, triglycerides, AST, and ALT were significantly reduced, and HDL cholesterol significantly increased, in both MHO and IRO subjects with no differences in percent changes from baseline. Insulin sensitivity increased in both MHO and IRO group. Insulin secretion was significantly reduced in the IRO group only. However, the disposition index significantly increased in both MHO and IRO individuals with no differences in percent changes from baseline between the two groups. The change in insulin sensitivity correlated with the change in BMI (r = −0.43; P<0.0001). In conclusion, our findings reinforce the recommendation that weight loss in response to LAGB intervention should be considered an appropriate treatment option for morbidly obese individuals regardless of their metabolic status, i.e. MHO vs. IRO subjects.     

Incident cardiovascular disease events in metabolically benign obese individuals

Nearly one-third of obese individuals are classified as metabolically benign; however whether this subgroup is at a lower risk of cardiovascular disease (CVD) is unclear. Using pooled data from the Atherosclerosis Risk in Communities and Cardiovascular Health Studies, we assessed incident CVD (coronary heart disease and stroke) using three definitions of the metabolically benign phenotype: (i) the ATP-III metabolic syndrome definition (≤2 of the ATP-III components, excluding abdominal obesity (ii) the expanded ATP-III definition (≤1 of: any ATP-III components, insulin resistance (IR), or systemic inflammation), and (iii) the IR-based definition (sex-specific lowest quartile of the HOMA(IR) distribution). The sample included 6,106 normal weight, 7,115 overweight, and 4,323 obese participants. Among obese, 27.0%, 18.1%, and 20.4% were metabolically benign by the three definitions, respectively. The CVD incidence rates (mean follow-up 11.8 years) were 7.1, 5.8, and 8.4 per 1,000 person-years in metabolically benign obese via the three definitions, respectively, compared to 14.3, 13.8, and 13.3 in at-risk obese, and 7.5, 6.7, and 8.2 in metabolically benign normal weight participants. Multivariable-adjusted hazard ratios of incident CVD in metabolically benign obese compared to their at-risk obese counterparts were 0.59 (95% CI 0.47-0.73), 0.52 (0.39-0.68), and 0.71 (0.57-0.90), respectively; and 1.24 (0.99-1.57), 1.16 (0.86-1.56), and 1.28 (1.01-1.62) compared to metabolically benign normal weight individuals. Only 28.7% of obese participants classified as metabolically benign by at least one definition were "metabolically benign" by all three definitions. Despite similar CVD risk estimates, the three definitions identified different subgroups of the obese population, perhaps suggesting distinct etiologies.     

Beta and alpha cell function in metabolically healthy but obese subjects: Relationship with entero‐insular axis

Objective:

Obesity is widely acknowledged as a critical risk factor for metabolic complications. Among obese subjects, there is a phenotype of metabolically healthy but obese (MHO) individuals that shows a favorable cardiometabolic risk profile. We aimed to evaluate the potential mechanisms underlying the metabolic profile of this subset, including alpha and beta cell function and entero‐insular axis.

Design and Methods:

One hundred twenty‐nine obese and 24 nonobese subjects were studied. Obese participants were defined as MHO or at‐risk obese, according to the homeostasis model of assessment‐insulin resistance (HOMA‐IR) index (MHO: lower tertile of HOMA‐IR, n = 43; at‐risk: upper tertile of HOMA‐IR index, n = 41). Insulin, glucagon, and incretin responses after a 120′ oral glucose tolerance test (75‐g OGTT) were investigated.

Results:

During OGTT, MHO individuals showed in comparison with at‐risk subjects: lower fasting and afterloads plasma levels of glucose, insulin, and C‐peptide; higher disposition index; lower fasting (P = 0.004) and at 30′ (P = 0.01) plasma glucose‐dependent insulinotropic polypeptide (GIP) levels; lower area under the curve (AUC) (0‐30) for GIP (P = 0.008); higher glucagon‐like peptide‐1 (GLP‐1) plasma levels at 90′ (P = 0.02) and 120′ (P = 0.02); lower glucagon plasma levels at baseline (P = 0.04) and at 30′ (P = 0.03); and appropriate glucagon suppression after the oral glucose load.

Conclusions:

MHO subjects show, as well as normal‐weight individuals, a lower diabetogenic profile by virtue of higher disposition index and unaffected entero‐insular axis. At‐risk obese individuals present increased GIP levels that might play a role in determining increased glucagon secretion and inappropriate glucagon responses after glucose load, thus contributing to impaired glucose homeostasis.     

A study on variability of quantitative sensory testing in healthy participants and painful temporomandibular disorder patients

Objectives: Quantitative sensory testing has mainly used thresholds to evaluate somatosensory sensitivity so far. The variability of different measures from session to session has also been investigated, but the variability of the single individual measures of a threshold or subject-based reports has not been considered. This study aimed to investigate the potential value of threshold variability in one session as a measure of internal consistency in somatosensory function.

Methods: The standardized quantitative sensory testing battery developed by the German Research Network on Neuropathic Pain was performed bilaterally over the infraorbital, mental, and hand regions in 70 healthy and 22 temporomandibular disorder pain participants. Somatosensory variability was investigated by calculating the Coefficient of Variation of three to five repeated measures in one threshold determination. The influences of side, gender, site, age, and presence of pain on the somatosensory variability were evaluated.

Results: In the healthy participants, somatosensory variability was region dependent: hand?>?mental and/or infraorbital for CDT, WDT, HPT, MDT-N, MPT-Y, MPT-N, WUR, and MPS (p?≤?0.043), infraorbital?>?hand for VDT (p?=?0.001), mental?>?infraorbital for HPT and WUR (p?≤?0.001); and age dependent for WDT, TSL, CPT, HPT, MDT-Y, MDT-N, MPT-N, and WUR (p?≤?0.017). Gender and side had no main effect on variability (p?≥?0.136). The pain patients presented higher variability compared with healthy participants for TSL, MDT-N, MPT-Y, WUR, and PPT (p?≤?0.033).

Discussion: The somatosensory variability along with the threshold would be a more complete method to investigate the somatosensory disorders and underlying pain mechanisms. The correlation between pain duration and somatosensory variability should be studied further with different pain conditions.     

Atherogenecity of LDL and unfavorable adipokine profile in metabolically obese, normal-weight woman

Objective: The relationship of visceral adiposity with adipocytokines and low‐density lipoprotein (LDL) particle distribution and oxidation in Asian metabolically obese, normal‐weight (MONW) individuals has not been evaluated. We aimed to investigate the association between visceral adiposity and adipocytokines and cardiovascular disease (CVD) risk factors in MONW Korean women with normal glucose tolerance. Methods and Procedures: We examined the metabolic characteristics of 135 non‐obese (BMI <25 kg/m²) women aged 25–64 years. Twenty‐five women (BMI <25 kg/m² and visceral fat adiposity (VFA) ≥100 cm²) were classified as MONW and 25 women (BMI <25 kg/m² and VFA <100 cm²), pair‐matched for age, weight, height, and menopausal status, as control group. Plasma lipid profiles and adipocytokines were evaluated in these two groups. Results: MONW subjects had higher systolic (P < 0.05) and diastolic blood pressure (P < 0.005) and higher concentrations of triacylglycerol (TG) (P < 0.005), insulin (P < 0.01), and free fatty acid (FFA) (P < 0.05) than control subjects. There was no significant difference between two groups in LDL‐cholesterol (LDL‐C) concentrations; however, MONW subjects had smaller LDL particles (P < 0.01) and higher concentrations of oxidized LDL (ox‐LDL) (P < 0.05) compared with controls. Moreover, MONW subjects had higher concentrations of tumor necrosis factor‐α (TNF‐α) (P < 0.05), interleukin‐6 (IL‐6) (P < 0.05) and leptin (P < 0.05), and lower plasma adiponectin concentrations (P < 0.05). Higher intake of saturated fat with lower ratio of polyunsaturated fatty acids (PUFAs) to saturated fatty acids (SFA) and lower fiber intake than normal subjects were found in MONW women. Discussion: We found an unfavorable inflammatory profile and a more atherogenic LDL profile in MONW female subjects even in the absence of a known CVD risk factors. Moreover, MONW consumed more saturated fat and less fiber than the control group.     

Low-dose oral risperidone lengthened sleep duration in healthy participants

We examined the effects of low-dose oral risperidone (RIS) on nocturnal sleep in healthy participants. This study was performed in a placebo-controlled manner in 10 healthy male volunteers (mean age, 23.6 years), with administration of 0.5 mg of RIS oral solution or a placebo in the morning or evening for 2 consecutive days. Each night, polysomnography (PSG) was performed, and PSG data during non-rapid-eye movement (REM) sleep were processed by power spectral analysis. An evening administration of 0.5 mg RIS significantly increased total sleep time, sleep efficiency and sleep stage 3, and significantly decreased total waking time and waking after sleep onset (P < 0.05). A morning administration of 0.5 mg RIS significantly increased sleep stage 3 (P < 0.05). According to power spectral analysis, the evening administration of RIS significantly increased the theta power (P < 0.05) and decreased the beta power (P < 0.05) during non-REM sleep. The administration of 0.5 mg oral RIS increases sleep stage 3 and increases total sleep time following evening administration.

     

Development of metabolic syndrome components in adults with a healthy obese phenotype: A 3‐year follow‐up

Objective:

There is a lack of data on the progression from a healthy obese phenotype toward an unhealthy obese phenotype and the development of metabolic syndrome (MetS). Our aim was to assess the development of MetS 3 years after screening in centrally obese individuals with a healthy obese phenotype and to evaluate the usefulness of repeated screening.

Design and Methods:

Eighty‐eight individuals (mean age 47 years, 88% female) with central obesity as their only MetS component (ATP III criteria) at baseline screening were re‐evaluated for MetS status after 3 years.

Results:

At follow‐up, the cardiometabolic risk profile in centrally obese individuals with a healthy phenotype showed a tendency toward deterioration. Thirty‐two percent developed at least one additional MetS component, 7% had developed MetS. Nobody had developed type 2 diabetes. An increased triglyceride level (n = 16) and an increased blood pressure (n = 18) were the components most often present at follow‐up. The people developing additional MetS components had a lower education level compared with the group that preserved the healthy centrally obese phenotype (80 vs. 71% lower educated, P = 0.35). They also had slightly worse baseline levels of the risk factors.

Conclusion:

The number of centrally obese individuals developing an unhealthy phenotype in this relatively short follow‐up period emphasizes the need for a regular surveillance of cardiometabolic parameters in centrally obese individuals. However, it is questionable whether a repeated screening for type 2 diabetes every 3 years, as recommended by the American Diabetes Association, in this category of patients is appropriate.