Renal glucosuria is associated with lower body weight and lower rates of elevated systolic blood pressure: results of a nationwide cross-sectional study of 2.5 million adolescents.

BACKGROUND: Gene coding mutations found in sodium glucose co-transporters (SGLTs) are known to cause renal glucosuria. SGLT2 inhibitors have recently been shown to be effective hypoglycemic agents as well as possessing cardiovascular and renal protective properties. These beneficial effects have to some extent, been attributed to weight loss and reduced blood pressure. The aim of the current study was to evaluate the prevalence of renal glucosuria amongst a large cohort of Israeli adolescents and to investigate whether renal glucosuria is associated with lower body weight and lower blood pressure values. METHODS: Medical and socio-demographic data were collected from the Israeli Defense Force's conscription center's database. A cross-sectional study to evaluate the association between conscripts diagnosed as overweight [BMI percentiles of ≥ 85 and < 95 and obesity (≥ 95 BMI percentile)] and afflicted with renal glucosuria was conducted. In addition, we assessed the association of renal glucosuria with elevated diastolic and systolic blood pressure. Multinomial regression models were used. RESULTS: The final study cohort comprised 2,506,830 conscripts of whom 1108 (0.044%) were diagnosed with renal glucosuria, unrelated to diabetes mellitus, with males twice as affected compared to females. The adjusted odds ratio for overweight and obesity was 0.66 (95% CI 0.50-0.87) and 0.62 (95% CI 0.43-0.88), respectively. Adolescents afflicted with renal glucosuria were also less likely to have an elevated systolic blood pressure of 130-139 mmHg with an adjusted odds ratio of 0.74 (95% CI 0.60-0.90). CONCLUSIONS: Renal glucosuria is associated with lower body weight and obesity as well as with lower rates of elevated systolic blood pressure.

Renal glucosuria in schoolchildren: Clinical characteristics.

BACKGROUND: We conducted an annual urine glucose screening program at schools, and diagnosed schoolchildren with diabetes at an early stage of the disease. We also identified some cases of renal glucosuria (RG), based on positive urine glucose with normal glucose tolerance. METHODS: During 2000-2015, 3 309 631 schoolchildren participated in the screening program. The positive rate for glucosuria in the first test was approximately 0.1%, whereas on repeat urine test it was approximately 0.05%. In total 350 schoolchildren were positive for glucosuria on detailed examination. Oral glucose tolerance test (OGTT) was also used to evaluate glucose intolerance. RESULTS: One hundred and two schoolchildren (29.7%) were diagnosed with diabetes, whereas RG was identified in 246 (70.3%) with normal glucose metabolism. In regard to the characteristics of RG, the percentage of boys was 50.3%, and the mean age at diagnosis was 11.2 ± 2.4 years. Twenty-eight children (11.4%) were overweight (body mass index standard deviation score [BMI-SDS] > +2.0 SD), whereas five (2.0%) were underweight (BMI-SDS < -2.0 SD). First-degree family history was suspected in 176 cases (71.5%). All RG subjects had normal glucose tolerance in the absence of insulin resistance and decreased insulin secretion (homeostasis model assessment for ß-cell function, 78.8 ± 59.5%) on OGTT. CONCLUSIONS: RG is not rare in Japanese schoolchildren with glucosuria. This disorder seems to have a strong genetic background, and to involve less growth retardation and weight loss than expected despite continuous excretion of glucose in urine.

Renal glucosuria is not associated with atherosclerotic cardiovascular disease outcome in a general Japanese community.

BACKGROUND AND AIMS: Renal glucosuria is defined as the excretion of detectable amounts of glucose in the urine without diabetes or hyperglycemia. Few data exist regarding the prevalence of renal glucosuria and its clinical impact on atherosclerotic cardiovascular diseases. METHODS: This study included 47,842 subjects (16,913 men, 35.4%) aged ≥40 years who underwent the Japanese specific health checkup in Kanazawa City during 2014. We defined renal glucosuria as fulfillment of all of the following three criteria: 1) detectable glucosuria; 2) the absence of diabetes; 3) normal blood glucose (<110 mg/dl fasting, and <140 mg/dl non-fasting). The presence of renal glucosuria and of factors associated with atherosclerotic cardiovascular diseases, including coronary artery disease and stroke, was assessed. RESULTS: The criteria for renal glucosuria were met by 665 (1.4%) subjects. Significantly higher proportions of subjects with renal glucosuria exhibited coronary artery disease, stroke, or either outcome than those without (14.9% vs. 12.1%, p = 0.0305; 9.9% vs. 6.9%, p = 0.00255; 22.3% vs. 17.0%, p = 4.0 × 10-4, respectively), but multivariate logistic regression analyses revealed that renal glucosuria was not associated with coronary artery disease (odds ratio [OR] = 0.940, 95% confidence interval [CI] = 0.748-1.171, not significant), stroke (OR = 1.122, 95% CI = 0.853-1.453, not significant), or atherosclerotic cardiovascular diseases (OR = 1.122, 95% CI = 0.853-1.453, not significant). CONCLUSIONS: These results indicate that the prevalence of renal glucosuria in the Japanese general population was 1.4%, and that renal glucosuria was not associated with atherosclerotic cardiovascular diseases per se.

Clinical and Genetic Features of Patients With Type 2 Diabetes and Renal Glycosuria.

Context: A sodium glucose cotransporter 2 (SGLT2) inhibitor, which increases urinary glucose excretion, was reported to decrease blood glucose levels and deaths among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease. SLC5A2 and HNF1A mutations are associated with renal glycosuria, but their contributions to renal glycosuria in patients with T2DM are not well understood. Objective: To assess the clinical features of patients with T2DM and renal glycosuria and those with T2DM and low urinary glucose excretion (LUGE) and identify variants in the exons of SLC5A2 and HNF1A in patients with renal glycosuria and T2DM. Design: A total of 2044 Chinese patients with T2DM, including 64 patients with renal glycosuria and 58 patients with LUGE, were tested for their plasma and urine glucose concentrations after fasting. SLC5A2 and HNF1A exons were sequenced. Results: Compared with patients with LUGE, those with renal glycosuria were younger (P = 0.008), had lower body mass index (BMI) (P = 0.002) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values (P < 0.0001), and were less likely to have hypertension (P = 0.006). HOMA-IR and BMI were negatively associated with renal glycosuria after adjusting for age, sex, hypertension, and insulin therapy. One novel mutation (V359G) of SLC5A2 in 32 patients with renal glycosuria and one known mutation (R131W) of HNF1A in 28 nonobese patients with renal glycosuria were identified. Conclusions: These findings suggest that there are subtypes of T2DM characterized by different urinary glucose excretion and cardiovascular risk factors. SLC5A2 and HNF1A mutations partially explain renal glycosuria in patients with T2DM.

Angiotensin-converting enzyme inhibitors and glycosuria.

Renal glycosuria associated with the use of angiotensin-converting enzyme inhibitors has been previously reported in two patients. A third patient was studied who developed isolated glycosuria associated with lisinopril therapy. As in the two previously described patients, this patient had a normal serum glucose level, underlying hypertension, and onset of glycosuria between 2 and 16 weeks after initiation of therapy with an angiotensin-converting enzyme inhibitor. The patient had renal artery stenosis with elevated renin levels. Age, time until resolution of glycosuria, and a rise in serum creatinine level did not have a consistent relationship with glycosuria associated with angiotensin-converting enzyme inhibitor therapy. Since glycosuria was the only defect noted, without evidence of any other urinary solutes, angiotensin-converting enzyme inhibitors may exert an effect on the glucose-specific proximal tubule transport system.

Pregnancy associated with renal glucosuria.

On reviewing 17,647 pregnancies over a 6-year period, 291 of 17,229 singleton pregnancies were noted to be associated with renal glucosuria. On analyzing these 291 pregnancies in 277 women, renal glucosuria was more frequently observed in those women with blood group types A and B and less in those with blood group type O. The incidence of renal glucosuria in nulliparous women, 2.8%, was significantly higher than that in parous women, 1.1%. A significantly high incidence of prematurity, 25.0%, was noted in women who persistently spilled a large amount of glucose.

Is questionnaire information valid in the study of a chronic disease such as diabetes? The Nord-Trøndelag diabetes study.

STUDY OBJECTIVE: The aim was to validate information about diabetes mellitus collected by questionnaire in a large epidemiological survey. DESIGN: Questions on diabetes diagnosis, medical treatment for diabetes, diabetes duration, and hypertension treatment were selected from the Nord-Trøndelag health survey questionnaires. One of the municipalities was selected for the validation study. SETTING: The health survey 1984-86 addressed all inhabitants > or = 20 years of age in Nord-Trøndelag county, Norway; 76,885 (90.3%) of the eligible population participated in answering the question on diabetes. PARTICIPANTS: All inhabitants in the municipality answering "yes" to the question on diabetes (n = 169) and the persons with the same sex born closest before and after each diabetic patient and answering "no" to the diabetes question (n = 338) were included. MEASUREMENTS AND MAIN RESULTS: A very thorough search was made in the medical files of the general practitioners in the municipality for corresponding information. Compared to the files, diabetes was verified in 163 out of the 169. The commonest cause of discrepancy was renal glycosuria. One out of the 338 registered non-diabetic persons was found to have diabetes. Diabetic patients tended to overestimate diabetes duration significantly. Insulin treatment was verified in 19/20 (95%) and treatment with oral hypoglycaemic agents in all 44 with an affirmative questionnaire answer. A negative answer on insulin and oral hypoglycaemic agents was verified in 100% and 99% respectively. CONCLUSIONS: The concordance was considerably higher than in a comparable Norwegian study performed 10 years earlier. Patient administered questionnaires may be a very reliable source of information for epidemiological purposes in a well defined chronic disease such as diabetes mellitus.