Glycaemic control of insulin-dependent diabetes mellitus in Sudan: influence of insulin shortage

Diabetes Research and Clinical Practice 30 (1995) 43-52

ELSEVIER

Glycaemic control of insulin-dependent diabetes mellitus in Sudan: influence of insulin shortage Murtada N. Elbagir*a’b, Mohammed A. Eltomb, Hans Rosling”, Christian Bernea “Department of Internal Medicine, University Hospiral. S-751 85 Uppsala, Sweden b&abcrinology and Diabetes Research Center, Omdarman Teaching Hospital, Omdarman, cInternationdl

Child Health

(ICH)

Unit, Department

of Paediatrics,

University

Hospiral,

S&n

L/pp.&a,

Sweden

Received 17 November 1994;revision received 23 August 1995;accepted 27 September 1995

Abstract Insulin availability and routine diabetes care were cross-sectionally investigated in 122 (M/F; 59/63) insulindependentdiabetic patients aged6-60 years with 2 1 year duration using a structured questionnaire interview followed by a free conversation. Haemoglobin Alo blood glucose, and serum lipids were measuredin the fasting state to assess the metabolic control. Only 12% of the patients had acceptable glycaemic control (HbA,, < 7.5%). Increased age, shorter diabetes duration, and higher body mass index were associated with better metabolic control. Omission or reduction of the insulin dose was experienced by 51% of the patients due to insulin shortage. The interview data consistently indicated that insulin non-availability had induced poor compliance to therapy regimensand lack of motivation for optimum glycaemic control. Due to limited resources,most of the patients received insufficient diabetes care and education, leading to lower rates of clinic attendance (SS%),and dietary non-compliance (78.5%).Elevated haemoglobin A,, was associatedwith higher fasting blood glucose levels (P < O.OOl),serum triglycerides (P < O.OS),and urinary glucose (P < 0.001). Measurable fasting C-peptide was observed in 52.5% of the patients and was related to the age at diagnosis, and body massindex (P < 0.001 for both). There is a considerable potential to improve diabetes care and education practice, and if accessibility to insulin is simultaneously facilitated, the glycaemic control in Sudanesediabetic patients will improve. Keywords: Insulin-dependent diabetes mellitus; Insulin therapy; Haemoglobin A,,; Sudan

1. Introduction Diabetes mellitus is a growing health problem in the Sudan and other developing countries. Insulindependent diabetes mellitus (IDDM) is not un* Corresponding author, Tel.: +46 18 664349, Fax: +46 18 510133.

common in Sudanese children, and approximately 25% of adult diabetic patients attending the general hospital clinics require insulin [ 1,2]. A majority of these patients have been reported to be poorly controlled and exhibit a high prevalence of acute and chronic complications [3,4]. Good metabolic control was attained in only 12-15% of the patients in these studies. Children with IDDM were

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characterisedby extremely poor glycaemic control and a high mortality and morbidity [5]. Limited accessto insulin and non-compliance to diet and insulin regimens were considered to contribute most to the outcome. Insufficient knowledge, due to lack of patient education and self-care training programmes,as well as poor socio-economic conditions are likely to play a major role for poor glycaemiccontrol and the ensuing poor prognosis. The Task Force on Insulin Distribution [6], established by the International Diabetes Federation (IDF) found that insulin was available c 25% of the time in two African countries, Uganda and Tanzania. Sudan was not responding in this report, but a similar situation exists, reinforced by inadequate financial resources for health care. It was the purpose of this study to investigate factors that could influence the metabolic control and morbidity patterns of insulin-dependent diabetes mellitus in the Sudan with particular emphasis on insulin shortage. 2. Patients and methods 2.1. Patients

Data were collected during 7 months starting on January lst, 1992.The study includes 123 insulindependent diabetic patients (M/F; 59/64) from all age groups with a diabetes duration of ~1 year. Insulin dependence was defined as those who received insulin at diagnosis and continued to do so up to the time of this investigation. The patients were recruited from the out-patient clinics of the main general hospitals of three different States in the Sudan that provide medical servicesto patients referred from all parts. In Khartoum State, during a 4-month period, all patients who visited the out-patient diabetes clinic in Omdurman Teaching Hospital for regular control with their own doctor, acceptedto participate in the study (n = 78). In Kordofan State, Western Sudan, patients collect insulin directly from the pharmacy of the general hospital in the capital, Elobied, without being seenby a physician. All patients who came to collect insulin during a 2-month period were included (n = 29).

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In the Central State, all the patients who, during a l-month period, came for follow-up at the diabetes clinic of the general hospital in the capital, Wad-Meddeni, were also included (n = 16). 2.2. General procedure

The patients or an accompanying parent took part in an interview based on a structured questionnaire followed by a free conversation [7]. Patients were classified according to three socioeconomic indices (residence, occupation, and education) into three classes,upper, middle, and lower. The upper class identified patients who reside in big houses in residential areas of 2600 m*, had at least university education, and who were engagedin skilled jobs or business.The middle class identified those who reside in 400-500m* areas, with intermediate or secondary education, and engagedin unskilled jobs, and the lower class, which identified those residing in areas 1300 m*, had only primary education or none, and who were engagedin manual work or farming. A few patients who did not fulfil the criteria for a specific class,were classified according to the general understanding of the socio-economic status. Thus, subjects with little or no schooling, who were successfullyengagedin business and resided in first classhousing, were classified as upper class. The distribution of the patients among these classesprobably corresponds to that of the general population. However, the composition of the socio-economic classes has changed as a consequence of the rapid changes that have occurred during the last ten years, and no comparable data are available at present. Weight (kg) with indoor clothing and height (m) without shoes was used to calculate body mass index (BMI; kg/m*). Characteristics of the diabetic state, its mode of presentation and the frequency of diabetic ketoacidosis were noted. The current dietary prescription and compliance were asked for, as was the mode of insulin therapy, availability, and compliance with the insulin regimen. A complete physical examination of all patients was undertaken by one physician (MNE).

M. N. Elbagir et al. /Diabetes Research and Clinical Practice 30 (1995) 43-52

2.3. Biochemical analysis

Urine samples were examined for glucosuria, ketonuria and albuminuria using test strips (Redia Test@, Boehringer-Mannheim, Mannheim, Germany). Capillary blood glucose was measured after an overnight fast using portable reflectometers (Reflolux II@, Boehringer-Mannheim, Mannheim, Germany). Venous whole blood from all patients was drawn in EDTA-containing tubes for determination of haemoglobin A,,. Another sample was centrifuged and the serum was separatedwithin 2 h, stored and transported frozen at -20°C until analysed in Uppsala, Sweden. The serum C-peptide concentration [8] was determined in the fasting state (detection limit; 0.05 nmol/l). Serum cholesterol and triglyceride concentrations were determined enzymatically (Boehringer Mannheim, Mannheim, Germany) in a Monarch instrument. Serum HDL-cholesterol was isolated with a combination of preparative ultracentrifugation [9] and precipitation with a sodium phosphotungstate and magnesium chloride solution [lo]. Serum aspartate and alanine amino transferaseswere determined by routine methods at the Geriatric Clinic, Uppsala University (reference limit; <0.8 PkaffL). Haemoglobin Al, was determined with fast-performance liquid chromatography (referencelimit; 3.5-6.0%) [l 11.One female patient (4 years duration) was found to have an abnormal haemoglobin (HbC) and was excluded from the analysis. 2.4. Statistical analysis

Data were fed into a Macintosh computer (Statview@; Abacus, Inc., Berkeley, CA, USA). Participants with missing clinical or biochemical data were excluded only from the comparison for which there were missing data. Results are expressed as mean f S.D. unless otherwise specified. Comparison between two groups was performed using Student’s t-test and log transformation was applied where distributions were skewed. If, however, distributions were still not normal, the Mann-Whitney U-test was employed. Simple linear regression, or Spearman-Rank correlation, were used for normally and non-normally distri-

45

buted data, respectively. Comparisons of ~333 groups were made using contingency tables and Chi-square test. All tests were two-tailed, and a Pvalue < 0.05 was considered significant. 3. Results 3.1. Clinical and socio-economiccharacteristics

The median age of the 122 patients was 29 (range 6-60) years, and at diagnosis was 2 1 (range l-46) years (Fig. 1). The median duration of diabeteswas 8 (range l-3 1) years. The mean BMI in adults (2 19 years) was 21 i 4.1 kg/m2 (range 14.8-35). BMI was positively correlated with age and age at diagnosis (r = 0.30; P < 0.001 and r = 0.28; P < 0.005, respectively). There were no gender differences in age, age at diagnosis, or BMI. Of 105 patients, diabetes presented with classical symptoms in 75%, and in 25% the onset was with ketoacidosis. Seventeen patients were diagnosed during investigation for other medical problems. Ninety-two patients (75%) reported being admitted at least once to hospital for diabetic ketoacidosis, 37% of them were admitted more than three times. Seventy percent of the patients came from the lower socio-economic class, 20% from middle class, and only 10% were from the upper class. Twelve percent of 102 patients aged 2 19 years had not received any schooling, 34% had received primary schooling, 45% secondary schooling, and 9% university education. 3.2. Metabolic control

The mean HbAi, was 9.3 f 1.6% (range; 5.3-13.3%) and the mean fasting blood glucose (FBG) was 11.8 f 5.9 mmol/l (range; 0.9-28 mmol/l). Fig. 2 depicts the distribution of HbA,, and FBG in males and females. Patients were classified into three groups according to the degree of metabolic control as evaluated by HbAi, level: good (group I: < 7.5%), unsatisfactory (group II: 7.5-9.9%), and poor (group III: ~10%).

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hf. N. Elbagir et al. /Diabetes Researchand Clinical Practice 30 (199s) 43-52

% of patients 30 25 20 15 10 5 0 % of patients 30 25 20 15 10 5 0

Age (YW

5-9

lo-14

15-19 20-24 25-29 30-34 35-39 40-44 45-49

50-54 55-59

260

Age at diagnosis (yrs) Fig. 1. Distribution of patients according to age and age at diagnosis in males (white bars, n = 59) and females(shaded bars, n = 63). Panel A, age. Panel B, age at diagnosis.

Table 1 shows the relationship of clinical and biochemical variables to the degree of metabolic control. The mean age and mean diseaseduration in group III were significantly lower than in the other two groups. The mean FBG correlated positively to the mean HbA,,. HbA,, was inversely correlated to the BMI (r = -24; P c 0.001). The mean daily insulin dose had no association with diseaseduration, HbA,,, or FBG, but correlated inversely with age (r = -0.31; P < 0.001). No significant differences were observed for serum cholesterol and HDL cholesteropcholesterol ratio in relation to the degree of metabolic 1 control. Serum transferases were also within the reference limits in the three groups.

Table 2 shows the relation of somedemographic and clinical variables to the degree of metabolic control. Although there was no influence of insulin shortage on the metabolic control (Fig. 3), it was related significantly to the state of compliance to therapy instructions and the number of daily insulin injections (P c 0.05 for both). Diabetes education and selfcare training were not related to the metabolic control in our patients. Whereas the rate of clinic attendance was not related to HbA,, levels, patients who attended regularly (2 3 visits/year) had better fasting blood glucose (P c 0.05). Patients who had one or repeated attacks of diabetic ketoacidosis had higher HbAi, than those who had no attacks (P c 0.05). School-

47

M. N. Elbagir et al. /Diabetes Research and Clinical Practice 30 (1995) 43-52

% of patients

-A

<5

55.9

6 -6.9

7-7.9

8-8.9

of patients

9-?,sj

10-10.9

11-11.9

12-12.9

13-13.9

HbA1, ("J)

lo-i4.9 1519.9 2044.9 Fasting blood glucose (mmol/l) Fig. 2. Distribution of patients according to hemoglobin A,, and fasting blood gkose concentration in males (white bars, n = 59) and females (shaded bars, n = 63). Panel A, percentage hemoglobin A,,. Panel B, fasting blood glucose concentration.

ing and socio-economic classeswere not related to the metabolic control in this group of patients. Table 3 comparespatients grouped according to beta cell function, defined here as low C-peptide (s 0.23 nmol/l) and normal C-peptide groups (> 0.23 nmol/I). Significant differences were only observed for age at diagnosis (P < 0.05), and the BMI (P < 0.001). Tables 4 compares the mean daily insulin dose in the three metabolic groups in relation to the number of daily insulin injections. No significant difference was observed in insulin dose among pa-

tients who received one daily injection or among those who received multiple injections. However, in the whole material, the mean daily insulin dose was significantly higher in patients who received multiple daily doses (P < 0.005). 3.3, Management of diabetes 3.3.1. Insulin therapy Ninety-seven (79.5%) patients were using shortacting insulin combined with intermediate-acting (NPH), and 9% used pre-mixed insulin. Seven

48

M.N. Elbagir er al. /Diabetes Research and Clinical Practice 30 (1995) 43-52

Table I Comparison between three groups subdivided according to metabolic control in relation to some clinical and biochemical variables Variable

HbA,, (%)

P-value*

(group 1; <7.5%) (n = 15)

(group II; 7.5-9.90/u) (group III; r 10%) (n = 68) (n = 39)

Age (years) Sex (M/F) Age at diagnosis (years)

31.1 A 12.4 619 20.2 zt 8.4

30.9 f 9.1 32136 21.4 f 8.2

25.7 zt 12.3 21/18 18.6 zt 8.8

NS NS

Duration (years) Body mass index (kg/m*) Fasting blood glucose

11.1 l 9.0 21.2 l 3.0 6.4 A 4.5

9.5 f 6.0 21.1 l 4.0 11.4 * 5.3

7.0 zt 6.9 18.8 * 5.9 14.7 f 5.8

P < 0.05 P < 0.05 P = 0.mo1

0.5 f 0.4 0.8 zt 0.4 40 0

0.4 l 0.3 0.8 f 0.4 85.3 20.5

0.4 l 0.3 0.9 f 0.5 92.3 28.2

NS NS

P < 0.05

t-w

C-peptide (nmol/l) Insulin (W./kg) Glucosuria (%) Acetonuria (%)

P = o.ooo1

NS

Results given as mean f S.D. *P-values from x*-test.

(5.7%) patients used only short-acting insulin, and another seven used intermediate-acting or longacting insulin only. One C-peptide-negative, slightly over-weight (BMI; 28.9 kg/m2), male patient, from a low socio-economic background and with 10 years duration took 30 units of regular insulin as a single daily dose resulting in a haemoglobin A,, of 10.4%.This particular patient claimed not to have experienced any insulin shortage. Forty-six patients (38%) were not complying with the prescribed insulin regimen. In 41% of them reduction of insulin dose or number of injections was due to insulin shortage. Another 39% of thesepatients reduced their insulin due to senseof well-being without blood or urine glucose monitoring. No clear reason was given in 20% of these patients. The free conversation consistently revealed that insulin non-availability was a big concern for most patients. In fact, the diverse problems with acquiring insulin was much better elucidated through free conversation, than by the structured questionnaire. Most patients faced considerable difficulties in collecting insulin as its supply was erratic and in some remote areas it was totally lacking. A 30-

year-old male patient with 4 years of diabetes, was admitted to hospital in ketoacidosis, insulin was not available at the hospital, and his only vial of intermediate acting insulin was used for his management.Patients from small towns or villages had to travel more than 200 km to collect their insulin. Patients reported using one type of insulin instead of prescribed two types or taking a single daily dose instead of more than two prescribed doses. Somepatients reported taking oral hypoglycaemic agents without medical advice due to insulin shortage. 3.3.2. Diet and dietary habits Eleven patients (9%) had no dietary prescription or instruction to follow. Mean HbAi, in this group of patients did not differ from that in patients with dietary prescription (9.5 f 1.1% vs. 9.3 f 1.7%). Eighty-seven patients of those who had dietary prescription (78.4%) were not complying with the diet instruction; HbA,, in this group of patients was not different from those who were complying (9.6 f 2% vs. 9.2 f 2%). Reasons for non-compliance was inaccessibility to foods prescribed in 41.4%, inability to change food

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Table 2 Comparison between three groups subdivided according to metabolic control and someclinical and demographic variables Variable

Imulin

shortage

Group II (n =68)

Group III (n= 39)

II

63

26

13

48

38

56

34.5

55

26

12

55

33

16

58

26

57 54.5

30 34.5

21 14 6

57 45 65

21 41 29

22

67

II

(%)

Reduced or omitted insulin (n = 62) Never reduced or omitted insulin (n = 60) Therapy

Group I (n = 15)

regimen

(743)

Once daily (n = 84) Multiple (n = 38) Diabetes education Occasional (n = 103) Not any (n = 19)

9.5 18 (%)

Chic attendance(70) Regular (n = 67) 13 11 Only seldom (n = 55) (“/) None (n = 14) Primary (n = 49) Secondary

sehoolillg

(n = 49)

University (n = 9)

habits in 36.8%, loss of appetite, carelessnessand indifference in 14.90/a,and the prescription was not fully understood in 6.9%.

Insulin shortage

No insulin shortage

Fig. 3. Comparison between patients who experienced insulin shortage (n = 62) and those who did not (n = 60) id relation to the percentagehemoglobin A,, (%) (not significant, using Student’s r-test).

at this level as recently emphasisedby the results of the DCCT trial [ 121. The primary aim of this study was to identify the most important determinants of metabolic control. However, very few patients were really adequately Table 3 Comparison of the patients grouped according to the fasting Cpeptide concentration in relation to some clinical variables Variable

C-peptide (so.23 nmol/l) (n = 57)

C-peptide (>0.23 nmolA) (n =63)

Age(Y=N

28.4 f 9.8 18.4 zt 7.0

29.8 l 11.5 NS 22.0 f 9.1 P < 0.05

19.1 zt 3.7

21.4 f 5.3

P < 0.001

IO.1 l 7.5 9.5 l 1.5 Il.4 zt 6.0

7.8 f 6.0 9.1 f 1.7 12.1 zt 5.9

NS NS

0.9 f 0.5

0.8 f 0.3

NS

Age at diagnosis

P-value*

(year@

4. Discussion The present study emphasisesthe major problem with unsatisfactory glycaemic control in a majority of insulin-dependent diabetic patients in the Sudan. Good metabolic control (HbA], < 7.5%) in only 15 of 122 patients, is similar to previous reports [3]. High rates of acute and chronic complications are likely to follow from hyperglycaemia

Body mass index (kg/d Duration (years) HbA,, (%) Fasting blood ghlcose wmow Insulin (I.U./kg)

NS

Results given in mean f S.D. *P-values from Student t- or Mann-Whitney &tests.

50

MN.

Eibagir et al. /Diabetes Research and Clinical Practice 30 (1995) 43-52

Table 4 Comparison of the three metabolic groups in relation to the daily insulin dose (mean * SD.) and number of injections N&&r of injections

Once daily (n=lM) Two or more (n = 38)

Insulin (I.U./kg) Group I

Group II*

Group III

0.7 f 0.3

0.7 l 0.4

0.9 f 0.4

0.9 f 0.4

1.0 f 0.3

I.1

l

0.8

‘Significant difference in the daily insulin dose using MannWhitney &test, P < 0.001.

controlled, and the results indicate a number of shortcomings in diabetes management,which contributed to the overall high glycaemic levels. Despite reports of problems with insulin availability from many patients, the discontinuous supply was not associatedwith the metabolic control, as assessedby HbAi,. Apart from the fact that insulin shortage for many patients had occurred prior to a time likely to have influenced the actual HbAi, concentration, this lack of association may have a more general explanation. Due to erratic supplies of insulin, patients more or less continuously took the minimum dose of insulin for survival and thus accepted this unsatisfactory glycaemic control. From the free conversations, it becameclear that most patients were indifferent to optimum metabolic control and responded passively towards irregular availability of the drug. Patients without endogenous insulin secretion and with grave problems with insulin availability may have died from ketoacidosis, which is reported to be a serious problem in the Sudan [5]. As this study was not designed to quantify the effectsof diabeteseducation on glycaemic control, the lack of association between these two elements cannot be fully interpreted. Nevertheless, due to the limited resources, our patients received little education in the busy clinic atmosphere. Moreover, improving the knowledge of the patient is unlikely to improve the metabolic control unless associatedwith continuous insulin supplies.

The finding that the number of daily insulin injections was not related to the metabolic control is not surprising. This factor does not influence the metabolic control unless associated with proper education and adequate glucose monitoring. Several studies have shown that insulin twice or three times a day improves metabolic control [ 131, whereasothers failed to do so [14]. However, patients with poor metabolic control might have preferred to take a single insulin injection instead of the prescribed two or more daily injections, or most probably they might have been receiving inadequateinsulin doses.Patients on single or multiple insulin doses were not different in relation to non-modifiable factors, such as age and disease duration, but were significantly different in relation to the insulin daily dose, a factor that did not influence HbA,,. Although the proportion of patients who reported poor compliance with dietary instructions was very high, no difference in the mean HbA,, between compliants and non-compliants was found (9.6 f 2.0 vs. 9.2 f 2.0%, respectively). The conventional sheetdiet instruction usually used for Sudanesediabetic patients has probably a limited impact on dietary knowledge or compliance as indicated by recent studies [15]. Even if there are conflicting data on the relationship between dietary compliance and metabolic control [16-181, a short-term intensified dietary education programme was found to be effective in Sudanese children and adolescentswith IDDM [19]. In Sudan, testing for fasting or postprandial blood glucose levels and urinary sugar determinations, although not always feasible, are the only methods used for assessmentof metabolic control. HbA,, is used only for research purposes. A significant correlation between HbA,, and FBG (r = 0.49) in this study is interesting and is not an invariable finding [20-231.At the very high fasting blood glucose levels observed, it is likely that the fluctuations are less and HbAi, would reflect the average blood glucose levels better. In contrast to studies in affluent countries [24], HbAi, was inversely correlated to patient age and diseaseduration (r = -0.22 for both; P < 0.05) in the Sudanesepatients. Low patient survival and poor compliance with treatment regimen of young

MN.

Elbagir et al. /Diabetes Research and Clinical Practice 30 (1995) 43-52

patients are probable explanations. Older patients with diabetes of long duration might have good knowledge and experience to deal with their diabetesand also a lessseverediseasewith preserved beta cell function. Beta cell function, as evaluated by fasting Cpeptide measurements,was not associatedwith the metabolic control in our patients. This finding is in accord with other studies [25,26]. In Sudanese diabetic children and adolescents, Elamin et al. [27], found an inverse correlation between fasting C-peptide and HbA,, concentration at the clinical onset of the disease. However, in other studies there was no obvious effect of residual beta cell function on glycaemic control in most patients with more than 5 years of diabetes [28,29]. Beta cell function was not related to the disease duration in this group of patients. Several studies have reported on the relation between diabetes duration and beta cell function in both IDDM and NIDDM [30,31]. In black patients with earlyonset diabetes and treated with insulin [32], an atypical clinical course has been observed. Fasting and peak levels of C-peptide were significantly higher than in a group of patients with IDDM, and no correlation was found between C-peptide levels and the disease duration. Conclusions drawn from the aforementioned studies may explain the lack of inverse correlation between beta cell function and diabetes duration in our study. In young Sudanesepatients, diabetes is mostly diagnosed on clinical grounds as IDDM, which might subsequently prove to be non-autoimmune diabetes, resembling maturity onset type of the young [32]. Misclassification of diabetes in young patients is associated with inappropriate therapy and consequent deterioration of glycaemic control. In a developing country like Sudan, misclassified diabeteswill negatively impact the fragile health system by undue occupancy of hospital beds and added pressure on the limited resources that are devoted mostly to infectious diseases. We conclude that the overwhelming majority of Sudanesepatients with IDDM are unsatisfactorily or poorly controlled, particularly those who are young and with short diseaseduration. Difficulties imposed by insulin shortage were encountered by most of the patients and emerged as a major

51

barrier to attain better compliance with insulin regimens.This problem is also likely to causepsychosocial disturbances and death from ketoacidosis. Due to insulin shortage, these patients seek survival as their target, instead of better control. This is alarming with respect to the risk of longterm complications. Therefore, every effort should be made to provide the patients with a continuous supply of insulin at reasonable cost. The present organisation of diabetes care does not give patients empowerment, knowledge, and self-careabilities. Well-trained diabetes teams and systematically organ&d diabetes care and education programmes would improve this situation. Acknowledgements This work was supported by grants from Indevelop Uppsala. We thank Bjiirn Kjellander, Boehringer-Mannheim, Scandinavia, Stockholm, for provision of the blood test strips. References 111Elamin, A., Omer, MIA., Hofvander, Y. and Tuvemo, T. (1989) Prevalence of insulin-dependent diabetes mellitus (IDDM) in school children in Khartoum, Sudan. Diabetes Care 12,430-432. 121EIMahadi, E.M.A., Salih, A.R. and Mukhtar, E. (1989) Patterns of diabetes mellitus in the Sudan. Trop. Grog. Med. 4, 353-355. 131 ELMahadi, E.M.A., Saeed,B.O., Atabani, G.S., ELHag, H.M. and Mukhtar, E. (1988) Assessmentof metabolic control in Sudanesediabetics using HbA,,. Sudan Med. J. 26, l-4. I41 ELMahadi, E.M.A., Kaballo and Mukhtar, E.A (1991) Features of non-insulin-dependent diabetes mellitus (NIDDM) in the Sudan. Diabetes Res. Clin. Pratt. 11, 59-63. [51 Elamin, A., Ahahir, H., Ismail B. and Tuvemo, T. Clinical pattern of childhood type I (insulin-dependent) diabetes mellitus in the Sudan. Diabetologia 35, 645-648. 161Deeb, L.C., Tan, M.H., Alberti and K.G.M.M. (1994) Insulin availability among International Diabetes Federation member associations: Report of the Task Force on Insulin Distribution. Diabetes Care 17, 220-223. 171 Lenore, M. and Peter, A. (1992) Can rapid anthropological proceduresbe applied to tropical diseases.Health Policy Plann. 7, 46-55. 181Heding, L.G. (1975)Radioimmunological determination of human C-peptide in serum. Diabetologia II, 541-548.

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[9] Havel, R.J., Eder, H.A. and Bragdon, J.H. (1955) The determination and chemical composition of ultracentrifugally separatedlipoproteins in human serum.J. Clin. Invest. 34, 1345- 1353. [IO] Siegler, L. and Wu, W.T. (1981) Separation of serum high-density lipoprotein for cholesterol determination: Ultracentrifugation vs precipitation with sodium phosphotungstate and magnesiumchloride. Clin. Chem. 27, 834-841. [I l] Jeppsson,J.O., Jerntorp, P., Sundkvist, G., Englund, H. and Nylund, V. (1986) Measurement of HbA,, by a new liquid-chromatographic assay: methodology, clinical utility and relation to glucose tolerance evaluated. Clin. Chem. 32, 1867-1872. [12] Diabetes Control and Complications Trial Research Group (DCCT) (1993).The effect of intensive treatment of diabetes on the development and progression of longterm complications in insulin-dependent diabetes mellitus. N. Et& J. Med. 329, 977-986. [13] Tchobroutsky, G., Charitansky, D., Blouquit, Y., Papoz, L., Soria, J. and Rosa, J. (1980) Diabetic control in 102 insulin-treated out-patients. Diabetologia 18, 447-452. (141 Boucher, B.J., Walton, C., Welch, S.G., Bamett, D., Yudkin, J.S. and Monson, J.P. (1980) Diabetic control on once- and twice-daily insulin injections. Diabetologia 19: 485. [15] McCulloch, D.K., Mitchell, R.D., Ambler, J. and Tattersall, R.B. (1983)Influence of imaginative teaching of diet on compliance and metabolic control in insulindependent diabetes. Br. Med. J. 287, 1858-1861. [16] Christensen,N.K., Terry, R.D., Wyatt, S., Pichert, J.W. and Lorenz, R.A. (1983) Quantitative assessmentof dietary adherence in patients with insulin-dependent diabetes mellitus. Diabetes Care 6, 245-250. [17] McCulloch, D.K., Young, R.J., Steel, J.M., Wilson, E.M., Prescott, R.J. and Dungan, L.J.P. (1983) Effect of dietary compliance on metabolic control in insulindependent diabetics. Hum. Nutrit. Appl. Nutrit. 37A, 287-292. [18] Tunbridge, S.R. and Wetherill, J.H. (1970) Reliability and cost of diabetic diet. Br. Med. J. 2, 78-80. [19] Elamin, A., Eltayeb, B., Hassan, M. and Tuvemo, T. (1992)Effect of dietary education on metabolic control in diabetic children attending a hospital clinic in Khartoum, Sudan. Acta Univ. Upsaliensis 348. (201 Tze, V.J., Thompson, K.H. and Leichter, J. (1978)

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HbA,, -an indicator of diabetic control. J. Pediatr, 93, 13 -16. [211 Gonen, 9. and Rubenstein, A.H. (1978) Haemoglobin Al and diabetes mellitus. Diabetologia 15, 1-8. 1221 Abraham, E.C., Huff, T.A., Cope, N.D., Wilson, J.B. Jr., Bransome, E.D. Jr. and Huisman, T.H.J. (1978) Determination of glycosylated haemoglobins (HbA,) with a new microcolumn procedure. Diabetes 27, 931-937. ~231 Lanoe, R., Soria, J., Thibult, N., Soria, C., Eshwege,E. and Tchobroutsky, G. (1977)Glycosylated haemoglobin concentrations and clinitest results in insulin-dependent diabetics. Lancet ii, 958-959. 1241 Dahlquist, G., Blom, P., Blom L. et al. (1982) Metabolic control in 131 juvenile-onset diabetic patients as measured by HbAt,: relation to age, duration, Cpeptide, insulin dose, and one or two insulin injections. Diabetes Care 5, 399-403. 1251 Madsbad, S., McNair, P., Faber, O.K., Binder, C., Christiansen, C. and Transbol, 1. (1980) Beta-cell function and metabolic control in insulin treated diabetics. Acta Endocrinol. 93, 196-200. 1261Ikeda, Y., Ando, N. and Ide, Y. (1975) B-cell function of insulin-dependent young onset diabetics assessedby Cpeptide immunoreactivity. Diabetologia 1I, 351-352. 1271 Elamin, A., Omer, MIA. and Tuvemo, T. (1992)lsletcell antibodies and endogenousinsulin secretion in Sudanese diabetic children. Diabetes Res. Clin. Pratt. 16, 91-96. WI Grajwer, L.A., Pildes, R. S., Horwitz, D.L. and Binder, C. (1977)Control ofjuvenile diabetes mellitus and its relationship to endogenous insulin secretion as measured by C-peptide immunoreactivity. J. Pediatr. 90, 42-48. 1291 Madsbad, S. (1983)Prevalenceof residual B-cell function and its metabolic consequences in type 1 (insulindependent) diabetes. Diabetologia 24, 141-147. 1301 Madsbad, S., Faber, O.K., Binder, C., McNair, P., Christiansen, C. and Transbol, 1. (1978)Prevalenceof residual beta-cell function in insulin-dependent diabetics in relation to age at onset and duration of diabetes. Diabetes 27, 262-264. [311 Lev-Ran, A. and Hwang, D.L. (1993) C-peptide in NIDDM. Diabetes Care 16, 76-81. 1321 Winter, W.E., Maclaren, N.K., Riley, W.J., Clarke, D.W., Kappy, M.S. and Spillar, R.P. (1987) Maturityonset diabetes of youth in black Americans. N. Engl. J. Med. 316, 285-291.