The Pathophysiology of Type 2 Diabetes Mellitus in Non-obese Individuals: An Overview of the Current Understanding

Olaogun, Idowu; Farag, Mina; Hamid, Pousettef

doi:10.7759/cureus.7614

Cited by 27 publications

(28 citation statements)

References 30 publications

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“…Autoimmune attack of insulin-generating pancreatic β-cells leads to the former type, whereas impaired compensation of β-cells leads to the latter type [ 19 ]. Two major animal models of type-2 diabetes, the obese and the non-obese, can mimic insulin resistance and β-cell failure [ 20 , 21 ]. Natural mutations, genetic manipulation, and high-fat feeding are used to develop the obese model.…”

Section: Discussionmentioning

confidence: 99%

Multi-strain probiotic supplement attenuates streptozotocin-induced type-2 diabetes by reducing inflammation and β-cell death in rats

Hsieh

Tsao

et al. 2021

PLoS ONE

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Probiotics are health beneficial bacterial populations colonizing the human gut and skin. Probiotics are believed to be involved in immune system regulation, gut microbiota stabilization, prevention of infectious diseases, and adjustments of host metabolic activities. Probiotics such as Lactobacillus and Bifidobacterium affect glycemic levels, blood lipids, and protein metabolism. However, the interactions between probiotics and metabolic diseases as well as the underlying mechanisms remain unclear. We used streptozotocin (STZ)-induced diabetic animal models to study the effect of ProbiogluTM, a multi-strain probiotic supplement including Lactobaccilus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, L. reuteri GL-104, and Bifidobacterium animalis subsp. lactis CP-9, on the regulation of physiochemical parameters related to type-2 diabetes. Experimental rats were randomly assigned into five groups, control group, streptozotocin (STZ)-treated rats (STZ group), STZ + 1× ProbiogluTM group, STZ + 5× ProbiogluTM group, and STZ + 10× ProbiogluTM group, and physiological data were measured at weeks 0, 2, 4, 6, and 8. Our results indicate that supplementation with ProbiogluTM significantly improved glucose tolerance, glycemic levels, insulin levels, and insulin resistance (HOMA-IR). Furthermore, we observed reduction in urea and blood lipid levels, including low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC). ProbiogluTM administration increased the β-cell mass in STZ-induced diabetic animal models, whereas it reduced the levels of proinflammatory cytokines TNF-α, IL-6, and IL-1β. In addition, the enhancement of oxidative stress biomarkers and superoxide dismutase (SOD) activities was associated with a decrease in malondialdehyde (MDA) levels. We conclude that ProbiogluTM attenuates STZ-induced type-2 diabetes by protecting β-cells, stabilizing glycemic levels, and reducing inflammation. Among all probiotic treating groups, the 10×ProbiogluTM treatment revealed the best results. However, these experimental results still need to be validated by different animal models of type-2 diabetes and human clinical trials in the future.

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Section: Discussionmentioning

confidence: 99%

Multi-strain probiotic supplement attenuates streptozotocin-induced type-2 diabetes by reducing inflammation and β-cell death in rats

Hsieh

Tsao

et al. 2021

PLoS ONE

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“… 31 In non-obese patients, abnormal fat pads accumulate in various parts of the body (ectopic fat deposition). 32 , 33 Higher levels of leptin secreted from adipocytes may reflect the increased abnormal fat correlated with microvascular complications. 33 Significant higher leptin levels can be observed in obese patients with T2DM.…”

Section: Discussionmentioning

confidence: 99%

“… 32 , 33 Higher levels of leptin secreted from adipocytes may reflect the increased abnormal fat correlated with microvascular complications. 33 Significant higher leptin levels can be observed in obese patients with T2DM. 34 We speculated that the binding between leptin and its receptors might tend to be saturated in the kidney of these patients, or the leptin receptors of kidney were not sensitive enough due to leptin resistance.…”

Section: Discussionmentioning

confidence: 99%

The Association Between Insulin Resistance, Leptin, and Resistin and Diabetic Nephropathy in Type 2 Diabetes Mellitus Patients with Different Body Mass Indexes

Huang

Peng

Dong

et al. 2021

DMSO

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This study aimed to compare HOMA-IR, leptin, and resistin as the risk factors for diabetic nephropathy in the type 2 diabetes mellitus (T2DM) patients with different BMI classifications. Materials and Methods: A total of 309 patients with T2DM were enrolled in this crosssectional study. All participants were divided into three groups according to BMI: the normal weight group (18.5 kg/m 2 ≤BMI<24 kg/m 2 ), the overweight group (24kg/m 2 ≤BMI<28 kg/m 2 ) and the obesity group (BMI≥28 kg/m 2 ). The clinical information and laboratory examinations were recorded in detail. Leptin and resistin levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: Higher HOMA-IR, leptin and resistin levels were found to be the risk factors for diabetic nephropathy when we made comparisons in the total population (P<0.05). In the normal weight group, logistic regression analysis showed that T2DM patients with higher HOMA-IR (OR=4.210, P=0.001), leptin (OR=2.474, P=0.031) and resistin levels (OR=8.299, P<0.001) had nearly 4-fold, 2-fold and 8-fold risk for diabetic nephropathy, respectively, after adjustments. The receiver operating characteristic (ROC) curves indicated that the area under the curves (AUCs) of HOMA-IR and resistin were 0.699 (95% CI 0.617-0.772) and 0.790 (95% CI 0.715-0.854), respectively, which were significantly larger than the AUC of 0.5 (all P<0.001). However, no significant association was observed between HOMA-IR, leptin, and resistin and renal complications (all P>0.05) in the overweight and obesity groups in both logistic regression and AUC analysis. Conclusion: Higher insulin resistance, leptin and resistin levels were observed as risk factors for diabetic nephropathy in T2DM patients with lower BMI. These were not obvious in the overweight and obese patients.

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“…Additionally, binge consumption of both HFD and EtOH promoted insulin resistance and glucose intolerance in the absence of an overweight phenotype. Clinically, such metabolic dysregulation in lean individuals is linked to increased risk for more severe type II diabetes as well as increased total and cardiovascular-related mortality compared with overweight diabetic individuals (George et al, 2015 ; Olaogun et al, 2020 ). Thus, there may be an unrecognized clinical population that may be seemingly healthy due to overall lower BMI but have underlying metabolic dysfunction that may not be fully considered.…”

Section: Behavioral and Physiological Outcomes By Diet Alcohol Andmentioning

confidence: 99%

Impact of High Fat Diet and Ethanol Consumption on Neurocircuitry Regulating Emotional Processing and Metabolic Function

Coker

Keller

Arnold

et al. 2021

Front. Behav. Neurosci.

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The prevalence of psychiatry disorders such as anxiety and depression has steadily increased in recent years in the United States. This increased risk for anxiety and depression is associated with excess weight gain, which is often due to over-consumption of western diets that are typically high in fat, as well as with binge eating disorders, which often overlap with overweight and obesity outcomes. This finding suggests that diet, particularly diets high in fat, may have important consequences on the neurocircuitry regulating emotional processing as well as metabolic functions. Depression and anxiety disorders are also often comorbid with alcohol and substance use disorders. It is well-characterized that many of the neurocircuits that become dysregulated by overconsumption of high fat foods are also involved in drug and alcohol use disorders, suggesting overlapping central dysfunction may be involved. Emerging preclinical data suggest that high fat diets may be an important contributor to increased susceptibility of binge drug and ethanol intake in animal models, suggesting diet could be an important aspect in the etiology of substance use disorders. Neuroinflammation in pivotal brain regions modulating metabolic function, food intake, and binge-like behaviors, such as the hypothalamus, mesolimbic dopamine circuits, and amygdala, may be a critical link between diet, ethanol, metabolic dysfunction, and neuropsychiatric conditions. This brief review will provide an overview of behavioral and physiological changes elicited by both diets high in fat and ethanol consumption, as well as some of their potential effects on neurocircuitry regulating emotional processing and metabolic function.

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The Pathophysiology of Type 2 Diabetes Mellitus in Non-obese Individuals: An Overview of the Current Understanding

Cited by 27 publications

References 30 publications

Multi-strain probiotic supplement attenuates streptozotocin-induced type-2 diabetes by reducing inflammation and β-cell death in rats

Multi-strain probiotic supplement attenuates streptozotocin-induced type-2 diabetes by reducing inflammation and β-cell death in rats

The Association Between Insulin Resistance, Leptin, and Resistin and Diabetic Nephropathy in Type 2 Diabetes Mellitus Patients with Different Body Mass Indexes

Impact of High Fat Diet and Ethanol Consumption on Neurocircuitry Regulating Emotional Processing and Metabolic Function

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