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Translating aetiological insight into sustainable management of type 2 diabetes.

ABSTRACT: Using a low-energy diet as a tool, it has been possible to elucidate the sequence of pathophysiological changes that lead to the onset of type 2 diabetes. Negative energy balance in type 2 diabetes causes a profound fall in liver fat content resulting in normalisation of hepatic insulin sensitivity within 7 days. As the period of negative energy balance extends and liver fat levels fall to low normal, the rate of export of triacylglycerol from the liver falls. Consequent to this, the raised pancreas fat content falls and in early type 2 diabetes, normal first-phase insulin secretion becomes re-established with normal plasma glucose control. This research, driven by the predictions of the 2008 twin cycle hypothesis, has led to a paradigm shift in understanding. Studying the reversed sequence of pathophysiological changes, the linked abnormalities in liver and pancreas have been revealed. Early type 2 diabetes is a potentially reversible condition. Surprisingly, it was observed that the diet devised as an experimental tool was actually liked by research participants. It was associated neither with hunger nor tiredness in most people, but with rapidly increased wellbeing. A defined period of weight loss followed by carefully planned weight maintenance-the 'One, Two' approach-has since been applied in clinical practice. Motivated individuals can reverse their type 2 diabetes and remain normoglycaemic over years. A large study is underway to evaluate the applicability of this general approach to routine primary care practice as a long-term management strategy.

SUBMITTER: Taylor R

PROVIDER: S-EPMC6448962 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBlood-based or urinary biomarkers may play a role in quantifying the future risk of type 2 diabetes (T2D) and in understanding possible aetiological pathways to disease. However, no systematic review has been conducted that has identified and provided an overview of available biomarkers for incident T2D. We aimed to systematically review the associations of biomarkers with risk of developing T2D and to highlight evidence gaps in the existing literature regarding the predictive and aetiological value of these biomarkers and to direct future research in this field.Methods and findingsWe systematically searched PubMed MEDLINE (January 2000 until March 2015) and Embase (until January 2016) databases for observational studies of biomarkers and incident T2D according to the 2009 PRISMA guidelines. We also searched availability of meta-analyses, Mendelian randomisation and prediction research for the identified biomarkers. We reviewed 3910 titles (705 abstracts) and 164 full papers and included 139 papers from 69 cohort studies that described the prospective relationships between 167 blood-based or urinary biomarkers and incident T2D. Only 35 biomarkers were reported in large scale studies with more than 1000 T2D cases, and thus the evidence for association was inconclusive for the majority of biomarkers. Fourteen biomarkers have been investigated using Mendelian randomisation approaches. Only for one biomarker was there strong observational evidence of association and evidence from genetic association studies that was compatible with an underlying causal association. In additional search for T2D prediction, we found only half of biomarkers were examined with formal evidence of predictive value for a minority of these biomarkers. Most biomarkers did not enhance the strength of prediction, but the strongest evidence for prediction was for biomarkers that quantify measures of glycaemia.ConclusionsThis study presents an extensive review of the current state of the literature to inform the strategy for future interrogation of existing and newly described biomarkers for T2D. Many biomarkers have been reported to be associated with the risk of developing T2D. The evidence of their value in adding to understanding of causal pathways to disease is very limited so far. The utility of most biomarkers remains largely unknown in clinical prediction. Future research should focus on providing good genetic instruments across consortia for possible biomarkers in Mendelian randomisation, prioritising biomarkers for measurement in large-scale cohort studies and examining predictive utility of biomarkers for a given context.

Project description:BackgroundIt has been established that careful diabetes self-management is essential in avoiding chronic complications that compromise health. Disciplined diet control and regular exercise are the keys for the type 2 diabetes self-management. An ability to maintain one's blood glucose at a relatively flat level, not fluctuating wildly with meals and hypoglycemic medical intervention, would be the goal for self-management. Hemoglobin A1c (HbA1c or simply A1c) is a measure of a long-term blood plasma glucose average, a reliable index to reflect one's diabetic condition. A simple regimen that could reduce the elevated A1c levels without altering much of type 2 diabetic patients' daily routine denotes a successful self-management strategy.MethodsA relatively simple model that relates the food impact on blood glucose excursions for type 2 diabetes was studied. Meal is treated as a bolus injection of glucose. Medical intervention of hypoglycaemic drug or injection, if any, is lumped with secreted insulin as a damping factor. Lunch was used for test meals. The recovery period of a blood glucose excursion returning to the pre-prandial level, the maximal reach, and the area under the excursion curve were used to characterize one's ability to regulate glucose metabolism. A case study is presented here to illustrate the possibility of devising an individual-based self-management regimen.ResultsResults of the lunch study for a type 2 diabetic subject indicate that the recovery time of the post-prandial blood glucose level can be adjusted to 4 hours, which is comparable to the typical time interval for non-diabetics: 3 to 4 hours. A moderate lifestyle adjustment of light supper coupled with morning swimming of 20 laps in a 25 m pool for 40 minutes enabled the subject to reduce his A1c level from 6.7 to 6.0 in six months and to maintain this level for the subsequent six months.ConclusionsThe preliminary result of this case study is encouraging. An individual life-style adjustment can be structured from the extracted characteristics of the post-prandial blood glucose excursions. Additional studies are certainly required to draw general applicable guidelines for lifestyle adjustments of type 2 diabetic patients.

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Translating aetiological insight into sustainable management of type 2 diabetes.

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