Comparative study on the efficacy of pioglitazone in Caucasian and Maori-Polynesian patients with poorly controlled type 2 diabetes.
OBJECTIVE
Although the pharmodynamic properties of the thiazolidinedione (TZD) insulin-sensitizing agents in the treatment of type 2 diabetes are well established, there are no studies comparing the pharmacoefficacy of these drugs in different ethnic groups. The aim of this pilot, prospective study was to examine the hypothesis that the efficacy of TZDs may vary depending on ethnicity. This aim was achieved by comparing the effects of 6-months treatment with pioglitazone (45 mg/day) on glucose control and metabolic and cardiovascular risk factors in Caucasian and Maori-Polynesian patients with poorly controlled type 2 diabetes.


METHODS
Ninety-seven patients (40 Caucasian and 57 Maori-Polynesian) with type 2 diabetes were selected for the study from our clinical databases if they were on the maximum tolerated dose of oral agents and had a haemoglobin A(1c) (HbA(1c)) > 8.0% for at least 2 months. All the patients received pioglitazone (45 mg/day) for 6 months in addition to their regular diabetes therapy. Clinical data and blood samples were collected at monthly intervals and the following indices measured: weight, blood pressure, oedema score, HbA(1c), plasma glucose, alanine amino transferase and adiponectin levels and plasma lipid profile, including low-density lipoprotein (LDL)-cholesterol particle size and atherogenic index of plasma (AIP). The data of the 81 patients who finished the study were analysed using analysis of variance, chi-square analysis and multiple regression methods.


RESULTS
The absolute change from baseline in mean HbA(1c) (Caucasian -1.4% vs. Maori-Polynesian -1.3%) and fasting glucose levels (Caucasian -2.1 mmol/l vs. Maori-Polynesian -2.8 mmol/l) was similar in the two groups. Pioglitazone caused an improvement in lipid profile in both ethnic groups, with a reduction in mean values of atherogenic fractions (triglyceride: Caucasian -0.5 mmol/l, p < 0.001 vs. Maori-Polynesian -0.3 mmol/l, p = 0.05; very low-density lipoprotein (VLDL)-cholesterol: Caucasian -0.11 mmol/l, p = 0.001 vs. Maori-Polynesian -0.04 mmol/l, p = 0.85; VLDL-triglyceride: Caucasian -0.36 mmol/l, p < 0.001 vs. Maori-Polynesian -0.22 mmol/l, p = 0.14; apolipoprotein B: Caucasian -0.09 mmol/l, p = 0.03 vs. Maori-Polynesian -0.08 mmol/l, p = 0.18). These changes were associated with an increase in LDL-cholesterol particle size (Caucasian +0.23 nm, p = 0.05 vs. Maori-Polynesian +0.26 nm, p = 0.04) and a decrease in AIP (Caucasian -0.14, p < 0.001 vs. Maori-Polynesian -0.08, p = 0.04). While the changes in the lipid indices tended to be greater in the Caucasian group, the difference in lipid response between the two ethnic groups was not statistically significant. Multiple regression analyses showed that the baseline value of the individual lipid fractions was the main determinant of the changes in lipid levels.


CONCLUSIONS
These results demonstrated that pioglitazone has similar beneficial effects on glucose control and plasma lipid profile in Caucasian and Maori-Polynesian patients with poorly controlled type 2 diabetes. Our data showed that while the improvement in lipid profile was more pronounced in Caucasian patients than in Maori-Polynesian patients, this difference was not statistically significant.
Shand
B
B
Lipid and Diabetes Research Group, Christchurch Hospital, Christchurch, New Zealand. brett.shand@cdhb.govt.nz
Scott
R
R
Connolly
S
S
Clarke
R
R
Baker
J
J
Elder
P
P
Frampton
C
C
Yeo
J
J
D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D000077205:Pioglitazone; D011114:Polynesia / Q000208:ethnology; D015203:Reproducibility of Results; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D044465:White People
D052242:Adiponectin; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D045162:Thiazolidinediones; D014280:Triglycerides