GLYCEMIC CONTROL, HYPERTENSION AND CHRONIC COMPLICATIONS IN TYPE 2 DIABETIC SUBJECTS ATTENDING A TERTIARY CARE CENTRE

Abdul Basit, Muhammad Zafar Iqbal Hydrie, Rubina Hakeem,

Mohammad Yakoob Ahmedani, Mohiuddin Waseem

Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Karachi, Pakistan.

Background: This study was carried out to assess the association of glycemic control and hypertension with chronic complications in type 2 diabetic subjects attending a tertiary care centre in Karachi, Pakistan. Methods: This was a cross sectional analytical study. First visit of type 2 diabetic subjects to the outpatient department of Baqai Institute of Diabetology and Endocrinology, from September 1996 to December 2001, were analyzed for this study. Socio-demographic attributes and clinical profiles were obtained from the computerized records of these patients retrospectively. Odds ratio with 95% confidence interval were reported for independent variables associated with outcome variables. Results: Records of 2199 subjects (48.5% males, 51.5% females) were analyzed. Mean age of the male and female subjects was 52.2 and 50.6 years respectively. Hypertriglyceridemia [OR: 1.74; 95% CI (1.18–2.57)] and diabetic foot ulcers [OR: 2.32; 95% CI (1.14–4.01)] were significantly associated with poor glycemic control according to HbA1c. Whereas hypertriglyceridemia [OR: 2.39; 95% CI (1.42 -4.03)] and hypertension [OR: 1.65; 95% CI (1.13–2.41)] were significantly associated with poor glycemic control according to FPG. Obesity [OR: 1.44; 95% CI(1.18–1.75)], Retinopathy [OR: 1.95; 95% CI(1.49–2.53)], nephropathy [OR: 1.99; 95% CI(1.45–2.75)],neuropathy [OR:1.40; 95% CI(1.15–1.71)] and presence of coronary arterial disease [OR:1.33; 95% CI(1.02–1.72) were found to be significantly associated with systolic blood pressure. Obesity [OR:2.07; 95% CI(1.69–2.54)], hyperglycemia [OR: 1.40; 95% CI(1.04–1.90)] and nephropathy [OR: 1.92; 95% CI(1.39 -2.64)] had significant association with high diastolic blood pressure. Conclusion: In conclusion this study shows the association of chronic complications with glycemic control and hypertension amongst type 2 diabetics in Karachi. This information needs to be verified by multicentred large scale studies in order to be helpful in planning healthcare and treatment strategies.

Keywords:     diabetes, complications, microvascular, macrovascular, Pakistan, hypertension,             glycemic control.


Introduction

Prevalence of type 2 diabetes is rising globally and the prevalence is reaching epidemic proportions in developing countries.1-2 The current  prevalence of diabetes in Pakistan is reported to be 8.6%, 11.1% and 13.9% according to World Health Organization (WHO) criteria for the provinces of Baluchistan, North West Frontier Province (NWFP) and Sindh respectively 3-5, our earlier study using the new American Diabetes Association (ADA) fasting criteria reported a prevalence rate of  7.2% in Hub area of Baluchistan.6 As regards diabetic complication rates in Pakistan the studies available are few in number  and need further comprehensive work.7-13

Furthermore, considerable data from epidemiological and interventional studies done in the developed countries have demonstrated the correlation of hyperglycemia with chronic diabetes complications.14-15 United Kingdom Prospective Diabetes Study (UKPDS) and Kumamoto study showed that tight glycemic control in type 2 diabetics reduced the risk of microvascular complications.16-17 A hypertensive subgroup analyzed in the UKPDS showed improvement in blood pressure provided benefit, both for macrovascular and microvascular outcomes.18

The present study therefore attempts to assess the association of glycemic control and hypertension with chronic complications in type 2 diabetic subjects attending a tertiary care centre in Karachi, Pakistan.

MATERIAL and Methods

It was a cross-sectional analytical study conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), a speciality diabetes care unit of Baqai University Hospital. A set of forms with incorporated parameters required for standard medical care of diabetes was used for recording information at the time of patients’ first visit to outpatient department (OPD).  For this study, computer coded records of the first visit of all type II diabetic subjects, older than 18 years, who visited the outpatient department of the Institute from September 1996 to December 2001 were analyzed without any breach of confidentiality regarding identification code as only minimal confidentiality or ethical issues were involved i.e. names were not disclosed anywhere and the researchers used only the computer code (identification code) of the patients.

Glycemic control was assessed by measuring glycosylated hemoglobin (HbA1c) by DiaSTAT Hemoglobin A1c Program, Bio-Rad or alternatively by fasting plasma glucose (FPG) estimated by glucose oxidase method.19 HbA1c levels of < 7% and >7% while FPG <110 mg/dl and >110 mg/dl were taken as good and poor indicators of glycemic control respectively. Enzymatic methods (GPO-PAP and CHOD-PAP) were used for total cholesterol, high density lipoproteins and triglycerides while low density lipoproteins (LDL) values were calculated.20 Total cholesterol  >200 mg/dl, triglycerides >150 mg/dl, low density lipoproteins >130 mg/dl while high density lipoproteins <40 mg/dl for males and < 50 mg/dl for females were taken as abnormal 21. Body mass index (BMI) was calculated by the standard formula and obesity was taken as BMI > 25 kg/m2 as suggested by the International Obesity Task Force.22

The fundus was examined using Vista 20 direct ophthalmoscope by a diabetologist. The retinopathy was classified as normal background  (presence of microdots and hard exudates), pre-proliferative and proliferative (presence of soft exudates and new vessels) or maculopathy.23 It also included subjects who had prior laser photocoagulation for diabetic retinopathy. Nephropathy  was defined as protein > 1+ on dipstick (Combur 10, Roche Diagnostics) with no other abnormal findings on urinary examination. Twenty-four hours quantitative analyses for proteinuria were not done routinely.24-25 Peripheral neuropathy was defined as absent touch or vibratory sensations of the feet.26 Touch sensation was assessed by 10 gm monofilament and vibration sensation by 128 Hz tuning fork.27 

Hypertension was defined as either B.P >130/85 mmHg or isolated systolic and diastolic blood pressure of greater than 130 and 85 mmHg respectively.28

Patients with history of coronary artery disease and stroke were taken as having macro vascular complication. Subjects with absent dorsalis pedis or posterior tibial pulses on examination with or without a history of intermittent claudication were labeled as having peripheral vascular disease (PVD). 

Data was entered on Microsoft Excel XP and then transferred to SPSS version 10 for statistical analysis. Independent sample t-test was used to asses the mean difference between continuous variables. Chi square test was performed to assess the statistical significance of difference in the proportions of any two groups. Odds ratios with 95% confidence interval were reported for independent variables associated with out come variables.

Results

Total subjects studied were 2199 in which 48.5% were males and 51.5% were females. Mean age of females (50 years ± 11.3) was lower than males (52 years ± 11.6) and this difference was statistically significant (P<0.003). Family history of diabetes was positive in 58% of the subjects.

Overall and categorical frequency of diabetic complications by gender is shown (Table 1)

In order to assess the association of various complications with glycemic control based on HbA1c was compared between subjects with or without complications (Table 2). Raised triglyceride levels and the presence of diabetic foot ulcer were significantly associated with poor glycaemic control. 

Association of glycaemic control on the basis of fasting plasma glucose was also assessed among subjects with or without complications (Table 3). High triglyceride levels and hypertension was significantly associated with poor glycaemic control.

Table 4 shows the association of systolic blood pressure of diabetic subjects with or without complications. Obesity, Retinopathy, neuropathy, nephropathy and presence of coronary arterial disease were found to be significantly associated with systolic blood pressure.

Association of various complications with diastolic blood pressure of subjects with or without complications was compared in table 5. Obesity, hyperglycemia and nephropathy had significant association with high diastolic blood pressure.

Discussion

The results of this study show the relative rates of various diabetes related chronic complications in subjects attending a tertiary care unit in Karachi, Pakistan and its association with hyperglycemia and hypertension in type 2 diabetic subjects.

Mean HbA1c values of 8.0% and 8.9% was seen in other south East Asian studies while mean HbA1c of 9.1% was found in our study.29,30 The association of glycemic control with microvascular complications was not evident in our study probably because of the cross-sectional design of our study, as is seen in various other studies (UKPDS, Wisconsin Epidemiologic Study and Kumamoto Study) in subjects with type 2 diabetes.

Table 1: Gender differences in diabetes related complications

Variables

Male

n (%)

Female

n (%)

Overall

n (%)

P value

Body Mass Index                      ≤25

                                                >25

408(48.3)

437(51.7)

316(34.4)

602(65.6)

724(41.1)

1039(58.9)

 

<0.001

Fasting Plasma Glucose            ≤110

                                                >110

67(11.2)

532(88.8)

70(11.2)

555(88.8)

137(11.2)

1087(88.8)

 

0.993

HbA1c                                    <=7%

                                                >7%

78(16.9)

383(83.1)

93(20.4)

362(79.6)

171(18.7)

745(81.3)

 

0.172

Cholesterol                              ≤200

                                                >200

276(56.6)

212(43.4)

245(51.3)

233(48.7)

521(53.9)

445(46.1)

 

0.098

Triglycerides                            ≤150

                                                >150

213(46.4)

246(53.6)

200(44.5)

249(55.5)

413(45.5)

495(54.5)

 

0.573

LDL                                         No

                                                Yes

203(61.1)

129(38.9)

183(59.6)

124(40.4)

386(60.4)

253(39.6)

 

0.692

HDL                                        No

                                                Yes

80(23.5)

261(76.5)

40(13.0)

268(87.0)

120(18.5)

529(81.5)

 

0.001

Retinopathy                             No

                                                Yes

842(82.1)

183(17.9)

938(85.9)

154(14.1)

1780(84.1)

337(15.9)

 

0.018

Nephropathy                           No

                                                Yes

356(67.8)

169(32.2)

335(76.1)

105(23.9)

691(71.6)

274(28.4)

 

0.004

Neuropathy                              No

                                                Yes

613(59.9)

410(40.1)

726(66.7)

362(33.3)

1339(63.4)

772(36.6)

 

0.001

Diabetic Foot Ulcer                  No

                                                Yes

917(85.9)

150(14.1)

1054(93.1)

78(6.9)

1971(89.6)

228(10.4)

 

<0.001

Hypertension                           No

                                                Yes

464(54.6)

386(45.4)

410(45.5)

491(54.5)

874(49.9)

877(50.1)

 

<0.001

Coronary artery disease            No

                                                Yes

896(84.0)

171(16.0)

970(85.7)

162(14.3)

1866(84.9)

333(15.1)

 

0.262

Stroke                                      No

                                                Yes

1021(95.7)

46(4.3)

1082(95.6)

50(4.4)

103(95.6)

96(4.4)

 

0.903

Peripheral arterial disease         No

                                                Yes

1014(95.0)

53(5.0)

1077(95.1)

55(4.9)

2091(95.1)

108(4.9)

 

0.906

Table 2: Association of HbA1c with various complications

Variables

HbA1c(≤7)

n (%)

HbA1c(>7)

n (%)

Odds ratio (95% CI)

Body Mass Index                      ≤25

                                                >25

63(37.7)

104(62.3)

265(37.1)

450(62.9)

 

1.03(0.73 – 1.46)

Cholesterol                              ≤200 

                                                >200

75(58.6)

53(41.4)

329(55.0)

269(45.0)

 

1.16(0.79 – 1.70)

Triglycerides                            ≤150

                                                >150

72(57.1)

54(42.9)

248(43.4)

324(56.6)

 

1.74(1.18 – 2.57)

LDL                                         No

                                                Yes

54(65.1)

29(34.9)

267(59.5)

182(40.5)

 

1.27( 0.78 – 2.07)

HDL                                        No

                                                Yes

13(15.5)

71(84.5)

84(18.5)

371(81.5)

 

0.81(0.43 – 1.53)

Retinopathy                             No

                                                Yes

144(85.2)

25(14.8)

605(83.1)

123(16.9)

 

1.17(0.73 – 1.87)

Nephropathy                           No

                                                Yes

70(75.3)

23(24.7)

251(70.3)

106(29.7)

 

0.78(0.46 – 1.31)

Neuropathy                              No

                                                Yes

108(64.3)

60(35.7)

441(60.7)

286(39.3)

 

1.17(0.82 – 1.66)

Diabetic Foot Ulcer                  No

                                                Yes

162(94.7)

9(5.3)

660(88.6)

85(11.4)

 

2.32(1.14 – 4.01)

Hypertension                           No

                                                Yes

74(45.7)

88(54.3)

321(45.9)

379(54.1)

 

0.99( 0.71 – 1.39)

Coronary artery disease            No

                                                Yes

147(86.0)

24(14.0)

643(86.3)

102(13.7)

 

1.03(0.64 – 1.66)

Stroke                                      No

                                                Yes

163(95.3)

8(4.7)

719(96.5)

26(3.5)

 

0.74(0.33 – 1.66)

Peripheral arterial disease         No

                                                Yes

161(94.2)

10(5.8)

718(96.4)

27(3.6)

 

0.61(0.29 – 1.28)

Table 3: Association of Fasting Plasma Glucose with various complications

Variables

FPG(≤110)

n (%)