| A substantial number of individuals have fasting plasma glucose lower than that required for the diagnosis of DM and plasma glucose during an oral glucose tolerance test (OGTT) intermediate between normal and diabetic levels. This group is now designated as having impaired glucose tolerance (IGT). The categorisation into normal, impaired glucose tolerance and diabetes mellitus is by 75 gms oral glucose tolerance test with WHO criteria as following.
Glucose Tolerance Test
| Fasting 2 hrs. |
Venous whole blood glucose mg/dl |
Venous plasma glucose |
| Normal |
IGT |
DM |
Normal |
IGT |
DM |
|
<100
<120
|
<120
120-170
|
<120
<180
|
<115
<140
|
<140
140-199
|
<140
<120
|
Impaired glucose tolerance stands between normalcy and diabetes or IGT and DM represents the two ends of a spectrum and in various studies there was no difference in the presence of various modifiable risk factors for macro vascular disease in the 2 states like HTN, smoking, obesity, alcohol ingestion and lack of physical exercise. Population with high percentage of IGT are likely to show an increase in the prevalence rate of DM in the future. It comprises a heterogeneous group of disorders which include
i. Syndrome X.
ii. Gestational Diabetes.
iii. Insulin resistance and
iv. Endocrinopathies.
While individuals with IGT are not considered diabetic, population studies have shown the following risks associated with IGT.
i. Progression to NIDDM.
ii. Increased risk for developing macrovascular complications,
iii. Paucity of microvascular complications such as nephropathy and retinopathy.
The state implies a risk with intervention there being a possibility that it is reversible. At the time of diagnosis of IGT, the subjects are asymptomatic. The presence of this entity in healthy and ambulatory individuals have prognostic implications and therefore should not be ignored.
Prevalence of IGT
There is great variability of IGT in different ethnic groups; eg. Pima Indians and Polynesians show higher IGT prevalence in population studies.
Table 1 : Impaired glucose tolerance amongst Indian populations
| in 30-64 yrs age group; based on a single OCTT |
Crude prei'alence % |
| |
|
Sample |
Size |
Male |
Females |
| 1989 |
South India |
Rural
Urban |
654
673 |
8.5
10.5 |
7.4
8.0 |
| 1984 |
South Africa
Tanzani |
Hindu
Muslim |
1203
1014
993 |
11.8
18.1
23.3
|
6.6
20.4
32.3
|
| 1987 |
Mauritius |
Hindu
Muslim |
1899
526 |
14.2
9.8 |
21.8
19.6 |
| 1985 |
Singapore |
|
166 |
5.9 |
2.5 |
| 1980 |
Fiji |
Rural Urban |
285 518 |
11.2
11.7 |
13.3 14.4 |
in 30-64 years age group, based on 2 elevated 2-hr OGTT blood
glucose values
1989 India Rural 5262 0.14
New Delhi 726 0.19
Trivandrum 1497 0.00
Ahmedabad 1572 0.28
Cuttack 1467 0.12
1989 Kalpa 469 0.48 2.30
1991 Bharangaham 2072 0.11 0.59
1991 Klang 438 5.56 5.83
1991 Enterprise 352 4.70 4.43
Rates of progression in various studies (Expressed in Percentage)
| Study |
No. of IGT |
Follow-up
in yrs |
Progressed
to NIDDM |
Reverted
to normal |
Remained
same |
1. USA study on
adult nonpregnant
female |
325 |
1-12 |
25 |
45 |
30 |
2. Burmingham
Diabetes survey
working party |
31 |
10 |
45 |
32 |
23 |
| 3. Bedford study |
241 |
10 |
15 |
53 |
23 |
| |
9% remained uncategori=ed |
| 4. Whitehall study |
204 |
5 |
13.2 |
5 |
81.8 |
IGT prevalence was less than o.5% in large standardised and uniform surveys conducted at 5 Indian centres in 1989 & 1991 and about 1% at Kalpa Village in Himalaya. In 1989 a South Indian study reported more than 8% of IGT prevalence among rural as well as urban subjects.
There were inconsistencies with decrease in IGT prevalence when oral glucose tolerance were repeated in some of the population. It is likely that ill defined and nonquantifiable physiological and psychological factors might influence the gut motility, glucose absorption and the release of gut factors which have varying impact on insulin secretion during the OGTT. The inconsistencies in OGTT could be attributable to these factors.
Natural course
As regards the natural history IGT subjects may have one of 3 courses.
1. Persistence of IGT
2. Reversal to normal glucose tolerance
3. Worsening to NIDDM
From reported studies the proportion of individuals with IGT who progress to NIDDM over a period of 10 years varies from 13 to 52% with a rate of progression of 1 to 12.5% per year.
| Studies |
No. of IGT |
Follow-up
in yrs |
Progressed to NIDDM |
Reverted to Normal |
Remained IGT |
| 1. Study on Pima Indians |
384 |
1.6-11.5 |
31 |
43 |
26 |
2. Study on
Nauruan subject |
51 |
6 |
26 |
39 |
35 |
These studies cannot be compared with each other. These studies were done in different population groups, selected in different ways and differing in method used and in the criteria adopted for defining worsening to DM. Nevertheless the single point emerged was that the levels of blood glucose themselves, however defined best predict worsening to DM.
Studies based on WHO definition of IGT with respect to methodology and criteria used, include the studies of natural history of IGT in Pima Indians and Nauruans, the population with highest prevalence of IGT and DM.
Risk factors for progression to NIDDM
Regarding the risk factors associated with progression to NIDDM in subjects with IGT, multitude of clinical and bio-chemical factors have been studied in the literature and include plasma glucose concentration at initial OGTT age, sex, "BMI, family history of DM, BP, Plasma insulin during OGTT, plasma lipids and serum creatinine. Single most important factor among these has been the plasma glucose concentration at initial OGTT. Less consistent factors include BMI and plasma insulin levels. In South African Indian subjects with IGT the risk of progression to NIDDM is total if baseline 2 hour plasma glucose islO.2 mmol/lit. or if plasma glucose is 7.3 mmol/lit. In mis population the BMI was significantly higher in subjects who progressed to NIDDM compared to those who did not. However BMI which was significant in univariate analysis failed to achieve significance in rnultivariate analysis. This finding is consistent with reported studies on other population.
In the South African studies in univariate analysis a positive history of paternal diabetes was significantly higher in subjects who progressed to NIDDM, although it lost significance in rnultivariate analysis. Family history of DM has not been found to be a predictive risk factor for worsening to DM in most of the studies in which it has been examined.
Most studies show that IGT is characterised by hyperinsulinemia (fasting & 2hrs levels) and insulin resistant. However their role in predicting progression to diabetes is not clear.
In Pima Indians those IGT subjects who progressed to NIDDM are characterised by higher baseline fasting insulin, lower post load 2 hrs insulin and lower post load insulin glucose ratio and lower post load ratio of increment of insulin to increment of glucose. This has been reported in 2 other studies also. It has also been found that proinsulin is significantly elevated in subjects with IGT. In some studies, the ratio of fasting proinsulin to fasting insulin was elevated in subjects with IGT.
Intervention needed or not?
There are so far only 3 studies as regards the effect that treatment has on IGT worsening to NIDDM. In one study none of the 23 subjects who were on a regimen of dietary restriction and tolbutamide progressed to DM. However in 2 other studies, (Whitehall and Bedford study) worsening to DM was not influenced by treatment which include carbohydrate restriction and phenformin.
On the basis of these studies a number of possible strategies may be implemented regarding the approach to management of subject with IGT,
These include
i. Observation without treatment but with followup OGTT yearly.
ii. Weight reduction by caloric restriction and exercise,
iii. Management of risk factors for CHD and hypertension.
iv. Drug treatment.
Diet, exercise and intervention treatment are effective methods to reduce the incidence of DM in IGT subjects. Weight loss in patients with clinically severe obesity prevent the progression of IGT to DM by more than 30 fold. Fat consumption significantly predicts NIDDM risk in subjects.
There is need for further population studies since, if intervention successfully alters the natural history of IGT, it would be a major public health achievement which would lead to reduction in the incidence of DM and perhaps also IHD.
REFERENCES
1. National diabetes data group. Classification and diagnosis of DM and other
categories of glucose tolerance. Diabetes 1979,28 1039-57.
2. WHO expert committee on Diabetes Mellitus 2nd report WHO Tech.Rep. Ser 1980,
646: 1-80.
3. Burmingham Diabetes Survey Working Party. Ten year follow-up on Burmingham
diabetes survey of 1961, Br. Med J. 1976:2:35-7.
4. Reaven GM Role of Insulin resistance in human disease. Diabetes 1988.37:1595-
1607.
5. Home P. The OGTT Gold that does not shine Diabetic Med. 1988,5:313-4.
6. Focus on Impaired Glucose Tolerance Diabetes Bulletin. International journal of
diabetes in developing countries Vol.16,1 lan-Mar, '1996.
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