Effects of the moderate LCD on glycemic control and cardiovascular risk factors
The baseline characteristics of the 124 patients are shown in . Interestingly, there were no significant differences between the analyzed patients and the 20 eligible patients excluded from study. The baseline characteristics of the excluded patients were 60.9 ± 11.2 years of age, 25.6 ± 3.8 BMI, 7.9% ± 1.1% HbA1c levels, and 3.1 ± 2.4 HOMA-IR. Of these 20 patients, 14 (70%) were normoalbuminuric, five (25%) were microalbuminuric, and one (5%) was macroalbuminuric at baseline.
Body mass index, glycemic control, serum lipid profiles, blood pressure, and drugs at baseline and 12 months in all patients (n = 124)
Compared with the baseline values, the mean HbA1c and FPG levels and the mean BMI significantly decreased after 12 months, from 7.9% ± 1.5% to 6.7% ± 0.6%, 151 ± 48 mg/dL to 130 ± 27 mg/dL, and 24.3 ± 3.7 to 23.5 ± 3.7, respectively (P < 0.001 for all parameters) (). The levels of other cardiovascular risk factors, such as IRI, HOMA-IR, and serum HDL cholesterol significantly improved (P = 0.003, P < 0.001, P = 0.001, respectively) among the patients treated with CARD for 12 months ().
At baseline, 44 of the 124 patients (35%) had already been prescribed antidiabetic drugs by other physicians. By the end of the study, 49 (40%) patients were taking antidiabetic drugs and these patients were typically prescribed a low dose of metformin and/or glimepiride ().
The number of patients taking metformin and the dosage of metformin both increased during the study period (). After excluding patients taking metformin, the mean HbA1c and FPG levels and the mean BMI and HOMA-IR significantly decreased (n = 99, P < 0.001 for all).
The number of patients on antidiabetic drugs apart from metformin, and/or the doses of these drugs taken, consistently decreased during the 12-month study period (). The proportion of patients on sulfonylureas decreased (for glibenclamide and nateglinide) or did not change (for gliclazide and glimepiride) during the 12-month study period and the mean daily dose of sulfonylureas per person tapered off. Three patients required a low dose of insulin therapy to achieve HbA1c levels of less than 6.5%.
Physical activity levels in two female patients (one normoalbuminuric patient and one microalbuminuric patient) increased during the study period despite our instructions; their increase in physical activity was no more than 1 hour of walking per day, 7 days per week, and 40 minutes of walking per day, 3 days per week, respectively.
Baseline characteristics of the normoalbuminuric, microalbuminuric, and macroalbuminuric patients
Of the 124 patients, 68 (55%) were normoalbuminuric, 50 (40%) were microalbuminuric, and six (5%) were macroalbuminuric at baseline (). The mean baseline UAE levels in the normoalbuminuric, microalbuminuric, and macroalbuminuric patients were 11 mg/g Cr (95% CI: 3, 47), 67 mg/g Cr (56, 80), and 945 mg/g Cr (234, 3802), respectively. The HbA1c and FPG levels were significantly higher in the microalbuminuric patients than in the normoalbuminuric patients ().
Baseline characteristics of patients by level of UAE (n = 124)
The patients showed relatively good compliance with the moderate LCD. The average total daily energy intake was 1734 ± 416 kcal/d (), and the average total daily energy intake per unit body weight was 28.4 ± 7.1 kcal/kg/d. The average daily intakes of carbohydrate, fat, and protein were 165 ± 51 g (38% ± 11% of total energy intake), 72 ± 30 g (37% ± 11% of total energy intake), and 81 ± 24 g (19% ± 4% of total energy intake), respectively (). The carbohydrates were mainly derived from rice (153 ± 97 g) and noodles (54 ± 68 g) made from wheat or buckwheat. Other carbohydrate sources included potatoes (19 ± 32 g), fruits (60 ± 80 g), bread (31 ± 35 g), confections (17 ± 24 g), and sugar (5 ± 6 g). The mean daily fiber intake was 14 ± 8 g.
Differences of dietary assessment, BMI, HbA1c, and HOMA-IR in less strict and strict CARD patients
Patients instructed to follow the less strict CARD regimen (n = 101), whose baseline HbA1c levels were <9.0%, consumed a diet of approximately 40% carbohydrate and 36% fat; whereas patients instructed to follow the strict CARD regimen (n = 23), whose baseline HbA1c levels were ≥9.0%, consumed a diet of approximately 33% carbohydrate and 42% fat (). There were significant differences in dietary %C (P = 0.010) and dietary percentage of energy from fat (%F) (P = 0.006) between the patients on the less strict CARD regimen and the patients on the strict CARD regimen (). The strict CARD regimen was associated with significant decreases in FPG concentrations (−66 ± 50 vs −10 ± 35 mg/dL, P < 0.001), HbA1c levels (−3.6 ± 1.4 vs −0.7% ± 0.7%, P < 0.001), and HOMA-IR (−1.6 ± 2.7 vs −0.4 ± 1.3, P = 0.001), compared with the less strict CARD regimen ().
Changes in UAE, eGFR, and other cardiovascular risk factors in the normoalbuminuric patients
In the group of patients with normoalbuminuria, two patients (3%) progressed to microalbuminuria over the course of 1 year (). One patient was an 83-year-old female with an 84-month history of diabetes, microhematuria, hypertension, and hyperlipidemia. The other patient was a newly diagnosed 51-year-old female with hypertension, hyperlipidemia, and rheumatoid arthritis, who was treated with prednisolone and methotrexate.
Figure 1 Individual changes in UAE (mg/g Cr) in (A) normoalbuminuric patients (n = 68), (B) microalbuminuric patients (n = 50), and (C) macroalbuminuric patients (n = 6), over 12 months. Dot lines show borderlines between normoalbuminuria and microalbuminuria (more ...)
The UAE significantly decreased by 20% (95% CI: 4, 33) during the 1-year study period (P = 0.021) (). The values for BMI, FPG, HbA1c, IRI, HOMA-IR, serum HDL cholesterol, and systolic and diastolic BP, significantly decreased after 12 months in the normoalbuminuric patients (). The eGFR did not materially decrease.
Changes in UAE, BMI, glycemic control, fasting serum insulin, serum lipid profiles, blood pressure, and eGFR over 12 months
Changes in UAE and other cardiovascular risk factors in the microalbuminuric and macroalbuminuric patients
Among the 50 patients with microalbuminuria, 26 (52%) underwent remission to normoalbuminuria during the follow- up period (). In contrast, one female patient (2%) progressed to macroalbuminuria. This patient was 68 years old and had hypertension, hyperlipidemia, and Wegener granulomatosis disease, and was treated with prednisolone.
The UAE significantly decreased in microalbuminuric by 53% (95% CI: 43, 62) during the 12-month study period (P < 0.001) (); the UAE decreased most (by 64% [95% CI: 51, 74]) in the hypertensive patients receiving olmesartan (n = 24). When patients taking olmesartan were excluded from consideration, the UAE still significantly decreased by 41% (n = 26, 95% CI: 25, 54, P < 0.001) and when patients taking either olmesartan or metformin were excluded, UAE significantly decreased by 40% (n = 24, 95% CI: 22, 54, P = 0.001). No significant difference was found between patients following less strict CARD (n = 35) (53%, 95% CI: 47, 64) and the patients following strict CARD (n = 15) (55%, 95% CI: 46, 68) (P = 0.89).
Additionally, in the macroalbuminuric patients, the UAE was significantly reduced by 41% (95% CI: 18, 57) over the 1-year period (P = 0.025) (). Two of the six patients achieved remission to microalbuminuria ().
In the microalbuminuric patients, the values for BMI, FPG, HbA1c, IRI, HOMA-IR, serum HDL cholesterol, and systolic BP significantly decreased (). The eGFR did not significantly decrease.
Correlation of Δ% UAE with changes in cardiovascular risk factors in microalbuminuric patients
The Δ% UAE was significantly and positively correlated with Δ HOMA-IR levels (rs = 0.308; P = 0.031) () but not correlated with changes in the other clinical variables. Moreover, the Δ% UAE was significantly and inversely correlated with baseline HOMA-IR levels (rs = −0.367; P = 0.009) and IRI levels (rs = −0.349; P = 0.013). The Δ HOMA-IR levels were strongly and inversely correlated with the baseline HOMA-IR levels (rs = −0.687; P < 0.001).
Correlation of Δ% UAE with Δ HOMA-IR in the 50 microalbuminuric patients.