scholarly journals Towards improved precision and a new classification of diabetes mellitus

2021 ◽  
Author(s):  
Emma Ahlqvist ◽  
Rashmi B Prasad ◽  
Leif Groop
Keyword(s):  
Insulin Resistance ◽  
Personalized Medicine ◽  
Fatty Liver ◽  
Early Stage ◽  
Age At Onset ◽  
Clinical Manifestations ◽  
Insulin Resistant ◽  
Increased Risk ◽  
Patient Health ◽  
The Right

Type 2 diabetes (T2D) is one of the fastest increasing diseases worldwide. Although it is defined by a single metabolite, glucose, it is increasingly recognized as a highly heterogeneous disease with varying clinical manifestations. Identification of different subtypes at an early stage of disease when complications might still be prevented could hopefully allow for more personalized medicine. An important step towards precision medicine would be to target the right resources to the right patients, thereby improving patient health and reducing health costs for the society. More well-defined disease populations also offer increased power in experimental, genetic and clinical studies. In a recent study, we used six clinical variables (GAD autoantibodies, age at onset of diabetes, HbA1c, BMI, and simple measures of insulin resistance and insulin secretion (so called HOMA estimates) to cluster adult-onset diabetes patients into five subgroups. These subgroups have been robustly reproduced in several populations worldwide and are associated with different risks of diabetic complications and responses to treatment. Importantly, the group with severe insulin-deficient diabetes (SIDD) had increased risk of retinopathy and neuropathy, whereas the severe insulin-resistant diabetes (SIRD) group has the highest risk for diabetic kidney disease (DKD) and fatty liver. This emphasizes the key role of insulin resistance in the pathogenesis of DKD and fatty liver in T2D. In conclusion, this novel sub-classification, breaking down T2D in clinically meaningful subgroups, provides the prerequisite framework for expanded personalized medicine in diabetes beyond what is already available for monogenic and to some extent type 1 diabetes.

scholarly journals Amygdala activation in maltreated children during pre-attentive emotional processing

2013 ◽  
Vol 202 (4) ◽  
pp. 269-276 ◽  
Author(s):  
Eamon J. McCrory ◽  
Stéphane A. De Brito ◽  
Philip A. Kelly ◽  
Geoffrey Bird ◽  
Catherine L. Sebastian ◽  
...  
Keyword(s):  
Psychiatric Disorder ◽  
Emotional Processing ◽  
Community Sample ◽  
Age At Onset ◽  
Childhood Adversity ◽  
Neural Response ◽  
Maltreated Children ◽  
Amygdala Activation ◽  
Increased Risk ◽  
The Right

BackgroundChildhood adversity is associated with significantly increased risk of psychiatric disorder. To date, functional magnetic resonance imaging (fMRI) studies of children have mainly focused on institutionalisation and investigated conscious processing of affect.AimsTo investigate neural response to pre-attentively presented affect cues in a community sample of children with documented experiences of maltreatment in the home.MethodA masked dot-probe paradigm involving pre-attentive presentation of angry, happy and neutral facial expressions was employed. Eighteen maltreated children were compared with 23 carefully matched non-maltreated peers.ResultsIncreased neural response was observed in the right amygdala for pre-attentively presented angry and happy faces in maltreated v. non-maltreated children. Level of amygdala activation was negatively associated with age at onset for several abuse subtypes.ConclusionsMaltreatment is associated with heightened neural response to positive and negative facial affect, even to stimuli outside awareness. This may represent a latent neural risk factor for future psychiatric disorder.

scholarly journals Female offspring born to obese and insulin-resistant dams are not at increased risk for obesity and metabolic dysfunction during early development

2018 ◽  
Vol 96 (1) ◽  
pp. 97-102 ◽  
Author(s):  
Hanin Aburasayn ◽  
Rami Al Batran ◽  
Keshav Gopal ◽  
Malak Almutairi ◽  
Amina Eshreif ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Female Offspring ◽  
Metabolic Dysfunction ◽  
Insulin Resistant ◽  
The Metabolic Syndrome ◽  
Rate Versus ◽  
Increased Risk ◽  
Study Completion ◽  
Reduced Rate

The percentage of women who are obese at the time of conception or during pregnancy is increasing, with animal and human studies demonstrating that offspring born to obese dams or mothers are at increased risk for obesity and the metabolic syndrome. Our goal was to confirm in an experimental model of metabolic syndrome in the dam, whether the offspring would be at increased risk of obesity. Conversely, we observed that male offspring born to dams with metabolic syndrome had no alterations in their body mass profiles, whereas female offspring born to dams with metabolic syndrome were heavier at weaning, but exhibited no perturbations in energy metabolism. Moreover, they gained weight at a reduced rate versus female offspring born to healthy dams, and thus weighed less at study completion. Hence, our findings suggest that factors other than increased adiposity and insulin resistance during pregnancy are responsible for the increased risk of obesity in children born to obese mothers.

scholarly journals Metabolic and nutritional approach to older frail people

2017 ◽  
Vol 3 (3) ◽  
Author(s):  
Stefano Volpato ◽  
Giovanni Zuliani
Keyword(s):  
Insulin Resistance ◽  
Intervention Studies ◽  
Large Body ◽  
Clinical Manifestations ◽  
Clinical Syndrome ◽  
Frailty Syndrome ◽  
Adequate Nutrition ◽  
Increased Risk ◽  
Prevention And Treatment ◽  
Pharmaceutical Interventions

Frailty is a common clinical syndrome in older adults that carries an increased risk for poor health outcomes including falls, incident disability, hospitalization, and mortality. It is characterized by multisystem dysregulations, leading to a loss of dynamic homeostasis, decreased physiologic reserve, and increased vulnerability to stressors. A large body of literature suggests several important multisystem pathophysiologic processes in the pathogenesis of the frailty syndrome, including chronic inflammation and immune activation, insulin resistance and those in musculoskeletal and endocrine systems. Currently, no effective pharmaceutical interventions have been developed for the prevention and treatment of the frailty syndrome. Conversely, epidemiological and intervention studies suggest that adequate nutrition and physical exercise might prevent or postpone the onset of frailty and related clinical manifestations.

Hemodynamic actions of insulin

1994 ◽  
Vol 267 (2) ◽  
pp. E187-E202 ◽  
Author(s):  
A. D. Baron
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Pressor Response ◽  
Physiological Role ◽  
Oxide System ◽  
Maximal Response ◽  
Insulin Resistant ◽  
The Right

There is accumulating evidence that insulin has a physiological role to vasodilate skeletal muscle vasculature in humans. This effect occurs in a dose-dependent fashion within a half-maximal response of approximately 40 microU/ml. This vasodilating action is impaired in states of insulin resistance such as obesity, non-insulin-dependent diabetes, and elevated blood pressure. The precise physiological role of insulin-mediated vasodilation is not known. Data indicate that the degree of skeletal muscle perfusion can be an important determinant of insulin-mediated glucose uptake. Therefore, it is possible that insulin-mediated vasodilation is an integral aspect of insulin's overall action to stimulate glucose uptake; thus defective vasodilation could potentially contribute to insulin resistance. In addition, insulin-mediated vasodilation may play a role in the regulation of vascular tone. Data are provided to indicate that the pressor response to systemic norepinephrine infusions is increased in obese insulin-resistant subjects. Moreover, the normal effect of insulin to shift the norepinephrine pressor dose-response curve to the right is impaired in these patients. Therefore, impaired insulin-mediated vasodilation could further contribute to the increased prevalence of hypertension observed in states of insulin resistance. Finally, data are presented to indicate that, via a yet unknown interaction with the endothelium, insulin is able to increase nitric oxide synthesis and release and through this mechanism vasodilate. It is interesting to speculate that states of insulin resistance might also be associated with a defect in insulin's action to modulate the nitric oxide system.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Lipodystrophies—Disorders of the Fatty Tissue

2020 ◽  
Vol 21 (22) ◽  
pp. 8778
Author(s):  
Birgit Knebel ◽  
Dirk Müller-Wieland ◽  
Jorg Kotzka
Keyword(s):  
Insulin Resistance ◽  
Fatty Liver ◽  
Molecular Mechanisms ◽  
Clinical Manifestations ◽  
Fat Distribution ◽  
Fat Cells ◽  
Fatty Tissue ◽  
Loss Of Function ◽  
Metabolic Complications ◽  
Crucial Difference

Lipodystrophies are a heterogeneous group of physiological changes characterized by a selective loss of fatty tissue. Here, no fat cells are present, either through lack of differentiation, loss of function or premature apoptosis. As a consequence, lipids can only be stored ectopically in non-adipocytes with the major health consequences as fatty liver and insulin resistance. This is a crucial difference to being slim where the fat cells are present and store lipids if needed. A simple clinical classification of lipodystrophies is based on congenital vs. acquired and generalized vs. partial disturbance of fat distribution. Complications in patients with lipodystrophy depend on the clinical manifestations. For example, in diabetes mellitus microangiopathic complications such as nephropathy, retinopathy and neuropathy may develop. In addition, due to ectopic lipid accumulation in the liver, fatty liver hepatitis may also develop, possibly with cirrhosis. The consequences of extreme hypertriglyceridemia are typically acute pancreatitis or eruptive xanthomas. The combination of severe hyperglycemia with dyslipidemia and signs of insulin resistance can lead to premature atherosclerosis with its associated complications of coronary heart disease, peripheral vascular disease and cerebrovascular changes. Overall, lipodystrophy is rare with an estimated incidence for congenital (<1/1.000.000) and acquired (1–9/100.000) forms. Due to the rarity of the syndrome and the phenotypic range of metabolic complications, only studies with limited patient numbers can be considered. Experimental animal models are therefore useful to understand the molecular mechanisms in lipodystrophy and to identify possible therapeutic approaches.

scholarly journals Exploring the Link between the Components of Metabolic Syndrome and the Risk of Depression

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Fang-Yih Liaw ◽  
Tung-Wei Kao ◽  
Ju-Ting Hsueh ◽  
Yi-Hsin Chan ◽  
Yaw-Wen Chang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Blood Chemistry ◽  
Assessment Method ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Increased Risk ◽  
Patient Health ◽  
Low Hdl ◽  
Apparent Association

Background.Metabolic syndrome (MetS) has been reported with an increased risk of depression. MetS was also associated with insulin resistance. This study aimed to evaluate whether MetS components might contribute to depression in participants with insulin resistance (IR) or not.Methods.This study included 3,331 participants ≥18 years in the NHANES 2009-2010. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). MetS components were measured using blood chemistry and body measurements. IR was identified using the homeostasis model assessment method.Results.Predicted PHQ-9 scores significantly increased as the number of MetS components increased in patients with IR. The adjustedβcoefficients of the predicted PHQ-9 score with 2, 4, and 5 MetS components were 1.803, 2.081, and 3.048, respectively (Pfor trend < 0.05). Low HDL-C levels were significantly associated with higher predicted total PHQ-9 scores in fully adjusted models in the IR group (P<0.05).Conclusion.The results indicated that the presence of a greater number of components of MetS was significantly associated with higher predicted total PHQ-9 scores in participants with IR. Among the components of MetS, the most apparent association was observed between low HDL and higher predicted total PHQ-9 scores.

scholarly journals Metabolic signature of obesity-associated insulin resistance and type 2 diabetes

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Haya Al-Sulaiti ◽  
Ilhame Diboun ◽  
Maha V. Agha ◽  
Fatima F. S. Mohamed ◽  
Stephen Atkin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Serum Samples ◽  
Metabolic Markers ◽  
Insulin Resistant ◽  
Increased Risk ◽  
Novel Biomarkers ◽  
Prospective Cohorts

Abstract Background Obesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain their insulin sensitivity and exhibit a lower risk of associated comorbidities. The underlying metabolic pathways differentiating obese insulin sensitive (OIS) and obese insulin resistant (OIR) individuals remain unclear. Methods In this study, 107 subjects underwent untargeted metabolomics of serum samples using the Metabolon platform. Thirty-two subjects were lean controls whilst 75 subjects were obese including 20 OIS, 41 OIR, and 14 T2DM individuals. Results Our results showed that phospholipid metabolites including choline, glycerophosphoethanolamine and glycerophosphorylcholine were significantly altered from OIS when compared with OIR and T2DM individuals. Furthermore, our data confirmed changes in metabolic markers of liver disease, vascular disease and T2DM, such as 3-hydroxymyristate, dimethylarginine and 1,5-anhydroglucitol, respectively. Conclusion This pilot data has identified phospholipid metabolites as potential novel biomarkers of obesity-associated insulin sensitivity and confirmed the association of known metabolites with increased risk of obesity-associated insulin resistance, with possible diagnostic and therapeutic applications. Further studies are warranted to confirm these associations in prospective cohorts and to investigate their functionality.

P5299Epicardial obesity as a significant predictor of leptino and insulin resistance

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Ott ◽  
G A Chumakova
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Linear Regression Analysis ◽  
Clinical Manifestations ◽  
Visceral Obesity ◽  
Soluble Receptors ◽  
Correlation Relationship ◽  
Group 2 ◽  
The Right

Abstract Leptino (LR) and insulin resistance (IR) are significant predictors of atherosclerosis, thrombosis, type 2 diabetes. The effect of epicardial obesity (EO) (as a type of visceral obesity) on the formation of LR and IR is studied. Objective To study the effect of EO on the formation of LR and IR among men with arterial hypertension (AH). Materials and methods The study included 130 men 49.5±4.3 years old, with AH of 1–3 degrees and the absence of clinical manifestations of coronary heart disease and atherosclerosis of other localizations, type 2 diabetes with a BMI of 20–35 kg /m2 and abdominal obesity according to WC ≥94 cm. Patients were divided into two groups depending on the thickness of epicardial adipose tissue (EAT), measured behind the free wall of the right ventricle by echocardiography. Group 1 consisted of 60 patients with epicardial obesity (EAT ≥7 mm), group 2 included 70 patients without epicardial obesity (EAT <7 mm). All subjects assessed indicators of LR and IR: measured levels of serum leptin (SL), soluble receptors for leptin (SLR), free leptin index (FLI), calculated as the ratio SL/SLR (as the only currently existing marker LR); IR was estimated by calculating the HOMA-IR index. IR was diagnosed with the generally accepted HOMA-IR index >2.7. Results When comparing LR indices in the studied groups, higher average values of SL, FLI were observed in the group with EO (EAT ≥7 mm) than in the group without EO (EAT <7 mm): (SL = 32.16 ng/ml (26.7; 37.62) versus SL = 14.92 ng/ml (11.62; 18.22), p=0.01, respectively); (FLI = 1.67 (0.47; 2.87) versus FLI = 0.37 (0.28; 0.46), p=0.01, respectively). Also in the EO group, higher indices of the HOMA-IR index were observed compared with the group without EO: (2.16 (1.62; 2.66) versus 1.35 (1.06; 1.64), p=0,01, respectively). When conducting the correlation analysis between FLI (as a marker of LR) and various obesity indicators (BMI, WC, EO) in the studied groups, a significant positive correlation relationship between FLI and EO was found in both the first and second groups (r=0.67, p=0.01; r=0.62, p=0.01, respectively). The IR index HOMA-IR also significantly positively correlated with EO in the group with a EAT ≥7 mm (r=0.68, p=0.01). BMI and WC did not correlate with FLI, IR in both groups 1 and 2 (p>0.05). In the EO group, 11 patients had IR with a HOMA-IR index >2.7. Using the linear regression analysis, the regression equation was obtained and the value of EO was calculated, from which the IR with HOMA-IR >2.7 started to be determined. This figure was 9.5 mm. Conclusions EO (EAT ≥7 mm) is a significant predictor of LR and IR, unlike the generally accepted criteria for obesity (BMI, WC). A EAT ≥9.5 mm can be a significant predictor of the development of type 2 diabetes, so these patients need additional examinations.

scholarly journals Insulin Resistance, the Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease

2005 ◽  
Vol 90 (3) ◽  
pp. 1578-1582 ◽  
Author(s):  
F. Angelico ◽  
M. Del Ben ◽  
R. Conti ◽  
S. Francioso ◽  
K. Feole ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Oral Glucose ◽  
Nonalcoholic Fatty Liver ◽  
Insulin Resistant ◽  
The Metabolic Syndrome

Background/Aims: An association of nonalcoholic fatty liver disease with the insulin-resistant metabolic syndrome has been suggested. The aim of the study was to assess the association of fatty liver to different degrees of insulin resistance and secretion. Methods and Results: The study was performed in 308 alcohol- and virus-negative consecutive patients attending a metabolic clinic, who underwent a complete clinical and biochemical work-up including oral glucose tolerance test and routine liver ultrasonography. Steatosis was graded as absent/mild, moderate, and severe. In nondiabetic subjects, a progressive (P &lt; 0.05) increase in mean homeostasis model of insulin resistance was recorded from the group without steatosis to the groups with mild/moderate and severe steatosis. Severe steatosis was associated with the clustering of the five clinical and biochemical features proposed for the clinical diagnosis of the metabolic syndrome. Subjects with the metabolic syndrome with a more pronounced insulin resistance had a higher prevalence of severe steatosis (P &lt; 0.01) compared with those with homeostasis model of insulin resistance below the median. Conclusions: The findings stress the heterogeneous presentation of patients with the metabolic syndrome when the diagnosis is based on the broad Adult Treatment Panel III clinical criteria and demonstrate that those who are more insulin resistant have a higher prevalence of severe steatosis.

scholarly journals Contrasting clinical manifestations of SDHB and VHL associated chromaffin tumours

2009 ◽  
Vol 16 (2) ◽  
pp. 515-525 ◽  
Author(s):  
Umasuthan Srirangalingam ◽  
Bernard Khoo ◽  
Lisa Walker ◽  
Fiona MacDonald ◽  
Robert H Skelly ◽  
...  
Keyword(s):  
Malignant Disease ◽  
Tumour Size ◽  
Age At Onset ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Catecholamine Secretion ◽  
Renal Cell Carcinomas ◽  
Von Hippel Lindau ◽  
Increased Risk ◽  
Multifocal Disease

Mutations in succinate dehydrogense-B (SDHB) and the von Hippel-Lindau (VHL) genes result in an increased risk of developing chromaffin tumours via a common aetiological pathway. The aim of the present retrospective study was to compare the clinical phenotypes of disease in subjects developing chromaffin tumours as a result of SDHB mutations or VHL disease. Thirty-one subjects with chromaffin tumours were assessed; 16 subjects had SDHB gene mutations and 15 subjects had a diagnosis of VHL. VHL-related tumours were predominantly adrenal phaeochromocytomas (22/26; 84.6%), while SDHB-related tumours were predominantly extra-adrenal paragangliomas (19/25; 76%). Median age at onset of the first chromaffin tumour was similar in the two cohorts. Tumour size was significantly larger in the SDHB cohort in comparison with the VHL cohort (P=0.002). Multifocal disease was present in 9/15 (60%) of the VHL cohort (bilateral phaeochromocytomas) and only 3/16 (19%) of the SDHB cohort, while metastatic disease was found in 5/16 (31%) of the SDHB cohort but not in the VHL cohort to date. The frequency of symptoms, hypertension and the magnitude of catecholamine secretion appeared to be greater in the SDHB cohort. Renal cell carcinomas were a feature in 5/15 (33%) of the VHL cohort and 1/16 (6%) of the SDHB cohort. These data indicate that SDHB-related tumours are predominantly extra-adrenal in location and associated with higher catecholamine secretion and more malignant disease, in subjects who appear more symptomatic. VHL-related tumours tend to be adrenal phaeochromocytomas, frequently bilateral and associated with a milder phenotype.

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