The classification of diabetes mellitus and the tests used for its diagnosis were brought into order by the National Diabetes Data Group of the USA and the second World Health Organization Expert Committee on Diabetes Mellitus in 1979 and 1980. Apart from minor modifications by WHO in 1985, little has been changed since that time. There is however considerable new knowledge regarding the aetiology of different forms of diabetes as well as more information on the predictive value of different blood glucose values for the complications of diabetes. A WHO Consultation has therefore taken place in parallel with a report by an American Diabetes Association Expert Committee to re-examine diagnostic criteria and classification. The present document includes the conclusions of the former and is intended for wide distribution and discussion before final proposals are submitted to WHO for approval. The main changes proposed are as follows. The diagnostic fasting plasma (blood) glucose value has been lowered to > or =7.0 mmol l(-1) (6.1 mmol l(-1)). Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for diabetes (plasma > or =6.1 to or =5.6 to <6.1 mmol l(-1)). Gestational Diabetes Mellitus (GDM) now includes gestational impaired glucose tolerance as well as the previous GDM. The classification defines both process and stage of the disease. The processes include Type 1, autoimmune and non-autoimmune, with beta-cell destruction; Type 2 with varying degrees of insulin resistance and insulin hyposecretion; Gestational Diabetes Mellitus; and Other Types where the cause is known (e.g. MODY, endocrinopathies). It is anticipated that this group will expand as causes of Type 2 become known. Stages range from normoglycaemia to insulin required for survival. It is hoped that the new classification will allow better classification of individuals and lead to fewer therapeutic misjudgements.

Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.

the growth of knowledge regarding the etiology and pathogenesis of diabetes has led many individuals and groups in the diabetes community to express the need for a revision of the nomenclature, diagnostic criteria, and classification of diabetes. As a consequence, it was deemed essential to develop an appropriate, uniform terminology and a functional, working classification of diabetes that reflects the current knowledge about the disease. (1)

Report of the expert committee on the diagnosis and classification of diabetes mellitus

A cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which occur together more often than by chance alone, have become known as the metabolic syndrome. The risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. Most recently, these have come from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The main difference concerns the measure for central obesity, with this being an obligatory component in the International Diabetes Federation definition, lower than in the American Heart Association/National Heart, Lung, and Blood Institute criteria, and ethnic specific. The present article represents the outcome of a meeting between several major organizations in an attempt to unify criteria. It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool. Three abnormal findings out of 5 would qualify a person for the metabolic syndrome. A single set of cut points would be used for all components except waist circumference, for which further work is required. In the interim, national or regional cut points for waist circumference can be used.

/pdf/harmonizing-the-metabolic-syndrome-a-joint-interim-statement-1vvpo24om1.pdf

Harmonizing the Metabolic Syndrome A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity

K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification

The metabolic syndrome has received increased attention in the past few years. This statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults.

The metabolic syndrome is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors —that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD).1 Patients with the metabolic syndrome also are at increased risk for developing type 2 diabetes mellitus. Another set of conditions, the underlying risk factors , give rise to the metabolic risk factors. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria to be used in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general they include a combination of both underlying and metabolic risk factors.

The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a pro-inflammatory state as well. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB), increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C). The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of ASCVD risk factors, but one that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to which components of the syndrome are …

https://www.lipidcenter.com/pdf/metabolic.pdf

Diagnosis and Management of the Metabolic Syndrome An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

As a possible model for the mechanism of precipitation of Reye's Syndrome in children the metabolic effects of oral aspirin were studied in normal subjects in the fasted and fed states, to determine whether aspirin altered fatty acid oxidation. Starvation increased blood 3-hydroxybutyrate concentrations, but aspirin had no effect on this or other metabolite concentrations in either the fasted or fed states.

The metabolic effects of aspirin in fasting and fed subjects: relevance to the aetiology of Reye's Syndrome

The aim was to establish whether risk factors for cardiovascular disease (CVD) are positively and independently associated with fasting insulin and/or body mass and waist-hip ratio in healthy elderly Nigerian subjects. Fasting plasma glucose, insulin, total cholesterol, triglycerides, blood pressure, and basal insulin resistance (HOMA method) were measured in 500 healthy elderly (> or = 55 years) Nigerian volunteers (295 men, 205 women). Associations between blood pressure, triglycerides or cholesterol and fasting insulin, HOMA, body mass index (BMI) or waist-hip ratio were examined using linear regression. Age was controlled for in all analyses. In men, diastolic and systolic blood pressure were strongly associated with BMI, while there was no evidence of an independent relationship with fasting insulin or HOMA. Triglycerides were strongly associated with waist-hip ratio, with a weaker independent association with HOMA but not fasting insulin; fasting insulin and HOMA showed strong independent associations with total cholesterol. In women diastolic and systolic blood pressure were also strongly associated with BMI, but there was an independent relationship with fasting insulin for diastolic blood pressure and a less significant (p = 0.057) one for systolic blood pressure. Triglycerides were significantly associated with BMI but none of the other variables; there were no significant associations with cholesterol. There was no evidence of interaction between fasting insulin or HOMA and BMI or waist-hip ratio. The results suggest the hypotheses that in this population BMI or waist-hip ratio are stronger determinants of blood pressure and triglyceride levels than fasting insulin or HOMA, and that where insulin does play a role its effects are separate and additive.

Are body mass or insulin resistance independently associated with cardiovascular risk factors in non-diabetic elderly Nigerians?

A glucose controlled insulin infusion system has been used during and after surgery for organic hyperinsulinism in a 37 year old woman. During surgery the system was used to monitor the blood glucose and, in order to avoid insulin hypersecretion, glucose was not infused. A strict correlation was observed between surgical procedures and metabolic behaviour, suggesting the resection of a microinsulinoma despite negative frozen section histology. After surgery plasma insulin was undetectable and an abnormal glycaemic level was observed during an IV glucose load. To ensure an adequate intake of fluid and calories 10% glucose was infused at a rate of 130 mg/min for 16h and blood glucose was clamped at 6.6 mmol/l by feedback insulin infusion. The gradual recovery of residual pancreatic tissue activity was demonstrated by the progressive decrease in exogenous insulin requirement, and confirmed by the normal glycaemic and insulinaemic response to an IV glucose load 20h after surgery.

Glucose controlled insulin infusion system (Biostator) application during surgery for a presumed pancreatic microinsulinoma.

The plasma GIP response to an oral 50 g glucose tolerance test has been compared in eight non-obese human subjects after 12 and 36 h of fasting. Basal plasma GIP and basal plasma insulin concentrations were similar after 12 and 36 h of fasting. Basal blood glucose was lower after 36 h fasting than after 12 h fasting (P<0.0125). After 36 h fasting the oral glucose tolerance test stimulated higher blood glucose concentrations at 60, 90 and 120 min (p<0.0125) and higher plasma insulin concentrations at similar time points (p<0.05), but stimulated plasma GIP concentrations were similar after 12 and 36 h fasts. These findings show that the increased insulinotrophic effect of oral glucose after 36 h fasting in nonobese subjects is not due to an associated augmentation of the glucose-induced GIP response.

/pdf/failure-of-fasting-to-influence-the-gip-response-to-oral-1f0ctk6ahm.pdf

Failure of fasting to influence the GIP response to oral glucose in non-obese human subjects

We have compared the action of human proinsulin and insulin on glucose turnover, intermediary carbohydrate, and lipid metabolism in insulin-dependent-diabetic (IDDM) subjects. Six, young, weight-matched (23 +/- 2 kg-2) IDDM subjects underwent separate hyperinsulinemic euglycemic clamps. Three, low dose, iv infusions of both insulin and proinsulin were used to construct dose response curves. The proinsulin infusions were chosen to give steady state levels approximately or equal to 20-fold higher on a molar basis than insulin, based on previous findings that proinsulin has only 5-10% the biological potency of insulin. Hepatic glucose production, measured using [6'6'2H2]glucose, was suppressed equally by proinsulin and insulin at the three dose levels; (I1) 2.8 +/- 0.7 (P1) 3.3 +/- 0.6, (I2) 2.3 +/- 0.9 (P2) 3.3 +/- 1.1, (I3) -2.0 +/- 1.7 (P3) -1.1 +/- 0.6 mumol/kg min-1. Percentage elevation of glucose disposal was significantly increased during the insulin infusions compared to proinsulin; (I1) 132 +/- 12 ...

K. G. M. M. Alberti

Papers

The metabolic effects of aspirin in fasting and fed subjects: relevance to the aetiology of Reye's Syndrome

Are body mass or insulin resistance independently associated with cardiovascular risk factors in non-diabetic elderly Nigerians?

Glucose controlled insulin infusion system (Biostator) application during surgery for a presumed pancreatic microinsulinoma.

Failure of fasting to influence the GIP response to oral glucose in non-obese human subjects

The effects of human proinsulin on glucose turnover and intermediary metabolism in insulin-dependent-diabetes mellitus.