Environmental exposure to cadmium (Cd) or lead (Pb) is independently associated with increased risks of type 2 diabetes, and chronic kidney disease. The aim of this study was to examine the effects of concurrent exposure to these toxic metals on the risks of diabetes and kidney functional impairment. The Cd and Pb exposure levels among study subjects were low to moderate, evident from the means for blood concentrations of Cd and Pb ([Cd]_b and [Pb]_b) of 0.59 µg/L and 4.67 µg/dL, respectively. Of 176 study subjects (mean age 60), 71 (40.3%) had abnormally high fasting plasma glucose levels. Based on their [Cd]_b and [Pb]_b, 53, 71, and 52 subjects were assigned to Cd and Pb exposure profiles 1, 2, and 3, respectively. The diagnosis of diabetes was increased by 4.2-fold in those with an exposure profile 3 (p = 0.002), and by 2.9-fold in those with the estimated glomerular filtration (eGFR) ≤ 60 mL/min/1.73 m² (p = 0.029). The prevalence odds ratio (POR) for albuminuria was increased by 5-fold in those with plasma glucose levels above kidney threshold of 180 mg/dL (p = 0.014), and by 3.1-fold in those with low eGFR) (p = 0.050). Collectively, these findings suggest that the Cd and Pb exposure profiles equally impact kidney function and diabetes risk.

Kidney disease associated with chronic cadmium (Cd) exposure is primarily due to proximal tubule cell damage. This results in a sustained decline in glomerular filtration rate (GFR) and tubular proteinuria. Similarly, diabetic kidney disease (DKD) is marked by albuminuria and a declining GFR and both may eventually lead to kidney failure. The progression to kidney disease in diabetics exposed to Cd has rarely been reported. Herein, we assessed Cd exposure and the severity of tubular proteinuria and albuminuria in 88 diabetics and 88 controls, matched by age, gender and locality. The overall mean blood and Cd excretion normalized to creatinine clearance (C_cr) as E_Cd/C_cr were 0.59 µg/L and 0.0084 µg/L filtrate (0.96 µg/g creatinine), respectively. Tubular dysfunction, assessed by β₂-microglobulin excretion rate normalized to C_cr(E_β2M/C_cr) was associated with both diabetes and Cd exposure. Doubling of Cd body burden, hypertension and a reduced estimated GFR (eGFR) increased the risks for a severe tubular dysfunction by 1.3-fold, 2.6-fold, and 84-fold, respectively. Albuminuria did not show a significant association with E_Cd/C_cr, but hypertension and eGFR did. Hypertension and a reduced eGFR were associated with a 3-fold and 4-fold increases in risk of albuminuria. These findings suggest that even low levels of Cd exposure exacerbate progression of kidney disease in diabetics.

Herbal medicine has been integrated into Thai culture for many centuries. However, studies on using herbal medicine in combination with antidiabetic agents for glycemic control in managing diabetes are limited. Herein, we aimed to assess the use of herbal medicines with different dosages of antidiabetic agents and their association with glycemic control in Thai patients with type 2 diabetes mellitus (T2DM). This hospital-based study included 739 patients with T2DM who consecutively visited four district hospitals in Thailand. An interviewer-administered questionnaire was used to collect patient-specific information, including hemoglobin A1c (HbA1c) levels. Chi-square and logistic regression analyses were used to assess associations and predictors, respectively. The prevalence of herbal medicine use was 37.5% (n = 264); 70.5% of the patients received information about herbal medicine usage for glycemic control from their relatives and friends, and 21 herbal plants were consumed in combination with their prescribed antidiabetic drugs. The use of herbal medicine was associated with the patients’ educational level (p = 0.001), income (p < 0.001), and duration of diabetes (p < 0.001). Good glycemic control (HbA1c < 7.0%) was associated with the use of bitter gourd in combination with 500 mg/day of the antidiabetic drug metformin (adjusted odds ratio = 8.33, 95% confidence interval = 1.04–66.49, p = 0.046). These patients were 2.92 times more likely to have good glycemic control than those who relied solely on 500 mg/day of metformin (adjusted OR = 2.921, 95% CI = 1.227–6.952, p = 0.015). The prevalence of herbal plant use was associated with different variables, including age, BMI, T2DM duration, and metformin dosage. Among the 21 herbal plants, the consumption of bitter gourd with 500 mg/day of metformin was associated with good glycemic control.

Regular use of Thai kratom has been linked to reduced blood triglyceride levels and body mass index (BMI) in healthy individuals. We analyzed Green Thai Kratom (GTK) and Red Thai Kratom (RTK) to investigate their effects on pancreatic digestive enzymes. The ethanol extracts of GTK and RTK inhibited lipase activity more strongly than alpha-glucosidase activity, suggesting the presence of lipase inhibitors. Mitragynine, the major compound in GTK, showed potent lipase inhibition and moderate alpha-glucosidase inhibition. Quercetin, found in both extracts, strongly inhibited alpha-glucosidase but had limited effects on lipase. These findings suggest that mitragynine and quercetin may hinder triglyceride and starch digestion. Combination inhibition studies revealed synergistic effects between mitragynine and quercetin on alpha-glucosidase activity. Additionally, both GTK and RTK extracts reduced fat accumulation in 3T3-L1 adipocyte cells, with quercetin specifically inhibiting Acetyl-CoA carboxylase 1 (ACC1), a key enzyme in fatty acid biosynthesis. Thus, GTK and RTK extracts, particularly mitragynine and quercetin, exhibit potential anti-obesity effects. We report the novel finding that Thai kratom inhibits de novo fatty acid synthesis by targeting ACC1, resulting in decreased fat accumulation in adipocytes. Regular use of Thai kratom in specific populations may improve blood triglyceride levels and reduce BMI by inhibiting lipase, alpha-glucosidase, and ACC1 activity. Further clinical trials are needed to determine optimal dosage, duration, toxicity levels, and potential side effects of Kratom use.

Cadmium (Cd) is a pervasive, toxic environmental pollutant that preferentially accumulates in the tubular epithelium of the kidney. Current evidence suggests that the cumulative burden of Cd here leads to the progressive loss of the glomerular filtration rate (GFR). In this study, we have quantified changes in estimated GFR (eGFR) and albumin excretion (E_alb) according to the levels of blood Cd ([Cd]_b) and excretion of Cd (E_Cd) after adjustment for confounders. E_Cd and E_alb were normalized to creatinine clearance (C_cr) as E_Cd/C_cr and E_alb/C_cr. Among 482 residents of Cd-polluted and non-polluted regions of Thailand, 8.1% had low eGFR and 16.9% had albuminuria (E_alb/C_cr) × 100 ≥ 20 mg/L filtrate. In the low Cd burden group, (E_Cd/C_cr) × 100 < 1.44 µg/L filtrate, eGFR did not correlate with E_Cd/C_cr (β = 0.007) while an inverse association with E_Cd/C_cr was found in the medium (β = −0.230) and high burden groups (β = −0.349). Prevalence odds ratios (POR) for low eGFR were increased in the medium (POR 8.26) and high Cd burden groups (POR 3.64). Also, eGFR explained a significant proportion of E_alb/C_cr variation among those with middle (η² 0.093) and high [Cd]_b tertiles (η² 0.132) but did not with low tertiles (η² 0.001). With an adjustment of eGFR, age and BMI, the POR values for albuminuria were increased in the middle (POR 2.36) and high [Cd]_b tertiles (POR 2.74) and those with diabetes (POR 6.02) and hypertension (2.05). These data indicate that (E_Cd/C_cr) × 100 of 1.44 µg/L filtrate (0.01–0.02 µg/g creatinine) may serve as a Cd threshold level based on which protective exposure guidelines should be formulated.