A glimpse of the 'natural history' of established Type 2 (non-insulin dependent) diabetes mellitus from the spectrum of metabolic and hormonal responses to a mixed meal at the time of diagnosis

Ismail, I.S. and Coates, P.A. and Ollerton, R.L. and Luzio, S.D. and Owens, D.R. (1994) A glimpse of the 'natural history' of established Type 2 (non-insulin dependent) diabetes mellitus from the spectrum of metabolic and hormonal responses to a mixed meal at the time of diagnosis. Diabetes Research and Clinical Practice, 26 (3). pp. 177-187. ISSN 0168-8227, DOI https://doi.org/10.1016/0168-8227(94)90059-0.

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Abstract

The reported glucose and immunoreactive insulin (IRI) responses to oral and intravenous glucose in subjects with Type 2 diabetes have not always been consistent. This may have resulted from variations in the method of glucose administration, the ethnic backgrounds of subjects, the diagnostic criteria applied, the duration of the disease or IRI assay methods. The use of a mixed meal rather than glucose has been shown to provide a more physiological stimulus to the pancreatic &cell due to both glucose and non-glucose secretagogues. We have analysed the metabolic and hormonal responses of 188 newly diagnosed Caucasian subjects with Type 2 diabetes and 38 non-diabetic subjects to a 500 kcal mixed meal. The diabetic subjects were stratified according to fasting plasma glucose (FPG)(<9,9- 12, 12-15 and _> 15 mmol/1) and body mass index (BMI) (<26.5, 26.5-30 and 30 kg/m²). Increasing FPG was associated with higher peak glucose concentrations and increasing failure to achieve basal glucose levels by 4 h. Median fasting IRI concentrations were similar to those of normal subjects, but all diabetic subjects had reduced early-phase insulin secretion. Diabetic subjects with FPG < 9 mmol/l showed augmented IRI area under the curve (AUC) at 2 and 4 h, whereas those with FPG > 9 mmol/l had progressive falls in IRI AUC to below that of the normal subjects (P < 0.0001 for the trend). Peak IRI concentrations declined progressively with increasing FPG. Despite equivalent glucose exposure simple trends of increasing AUC, IRI with increasing BMI were statistically significant (P < 0.001, P < 0.02, P < 0.001 and P < 0.01, respectively for each FPG group). Both fasting and AUC non-esterified fatty acid concentrations increased significantly with FPG regardless of BMI (P < 0.001 for the trends). These results using a more physiological mixed meal challenge in a large number of recently diagnosed Type 2 diabetic subjects demonstrate a marked and increasing loss of P-cell secretory function with increasing fasting hyperglycaemia aggravated by insulin resistance with increasing obesity.

Item Type:	Article
Funders:	UNSPECIFIED
Uncontrolled Keywords:	Mixed meal test; Metabolic/hormonal responses; Type 2 diabetes mellitus
Subjects:	R Medicine > R Medicine (General)
Divisions:	Faculty of Medicine
Depositing User:	Ms. Izzan Ramizah Idris
Date Deposited:	08 Dec 2014 04:25
Last Modified:	08 Dec 2014 04:25
URI:	http://eprints.um.edu.my/id/eprint/10429

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