Clinical outcomes in patients with type 2 diabetes mellitus-related kidney disease: A Jordanian population cohort study.

BACKGROUND: Diabetic kidney disease (DKD) increases the risk of cardiovascular (CV) complications, kidney disease progression, and mortality. We aimed to determine the incidence and risk of these outcomes according to DKD phenotype among the Jordanian population. METHODS: A total of 1172 type 2 diabetes mellitus patients with estimated glomerular filtration rates (eGFRs) of >30 ml/min/1.73 m2 were followed-up from 2019 to 2022. At baseline, patients were classified according to the presence of albuminuria (>30 mg/g creatinine) and reduced eGFR (<60 ml/min/1.73 m2) into four phenotypes: non-DKD (reference category), albuminuric DKD without decreased eGFR, non-albuminuric DKD with decreased eGFR, and albuminuric DKD with decreased eGFR. RESULTS: Mean follow-up was 2.9 ± 0.4 years. Overall, 147 patients (12.5 %) experienced CV events, while 61 (5.2 %) demonstrated kidney disease progression (eGFR: <30 ml/min/1.73 m2). The mortality rate was 4.0 %. Multivariable-adjusted risk for CV events and mortality was greatest for the albuminuric DKD with decreased eGFR group (hazard ratio [HR]: 1.45, 95 % confidence interval [CI]: 1.02-2.33 and HR: 6.36, 95 % CI: 2.98-13.59, respectively), with the risk increasing when adjusted for prior CV history (HR: 1.47, 95 % CI: 1.06-3.42 and HR: 6.70, 95 % CI: 2.70-16.60, respectively). Risk of a ≥40 % decline in eGFR was greatest for the albuminuric DKD with decreased eGFR group (HR: 3.45, 95 % CI: 1.74-6.85), followed by the albuminuric DKD without decreased eGFR group (HR: 1.6, 95 % CI: 1.06-2.75). CONCLUSION: Thus, patients with albuminuric DKD and decreased eGFR were at greater risk for poor CV, renal, and mortality outcomes compared to other phenotypes.

Diabetic kidney disease in patients with type 2 diabetes mellitus: a cross-sectional study.

AIM: Diabetic kidney disease (DKD) is a major long-term complication of diabetes mellitus (DM). Given the paucity of data on DKD in Jordan, we aimed to evaluate the prevalence, characteristics and correlates of DKD in Jordanian patients with type 2 DM. METHODS: This cross-sectional study included 1398 adult patients with type 2 DM who sought medical advice in the endocrinology clinic between March and September 2019. Demographic, clinical and laboratory data were reviewed. DKD was defined as reduced eGFR, and/or albuminuria. Three regression models were constructed to identify factors associated with CKD stages, albuminuria and DKD. RESULTS: Overall, 701 (50.14%) patients had DKD, with a median age of 59.71 ± 11.36  years. Older age, high triglycerides, and low high-density lipoprotein were associated with DKD (multivariable odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03, p < 0.01; OR: 1.1, 95% CI: 1.01-1.2; and OR: 0.98, 95% CI: 0.97-0.99, p < 0.01 respectively). Metformin and renin-angiotensin system blockers were negatively associated with albuminuria and chronic kidney disease stages (p < 0.01). CONCLUSION: Our study demonstrated that approximately one half of patients with type 2 DM had DKD. Further studies are necessary to understand this high prevalence and the underlying factors. Future research are needed to assess implementing targeted community-based intervention.

L-Citrulline Supplementation Increases Plasma Nitric Oxide Levels and Reduces Arginase Activity in Patients With Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is becoming a major contributor to cardiovascular disease. One of the early signs of T2DM associated cardiovascular events is the development of vascular dysfunction. This dysfunction has been implicated in increasing the morbidity and mortality of T2DM patients. One of the important characteristics of vascular dysfunction is the impaired ability of endothelial cells to produce nitric oxide (NO). Additionally, decreases in the availability of NO is also a major contributor of this pathology. NO is produced by the activity of endothelial NO synthase (eNOS) on its substrate, L-arginine. Reduced availability of L-arginine to eNOS has been implicated in vascular dysfunction in diabetes. Arginase, which metabolizes L-arginine to urea and ornithine, competes directly with NOS for L-arginine. Hence, increases in arginase activity can decrease arginine levels, reducing its availability to eNOS and decreasing NO production. Diabetes has been linked to elevated arginase and associated vascular endothelial dysfunction. We aimed to determine levels of plasma NO and arginase activity in (T2DM) patients and the effects of L-citrulline supplementation, a natural arginase inhibitor, on inhibiting arginase activity in these patients. Levels of arginase correlated with HbA1c levels in diabetic patients. Twenty-five patients received L-citrulline supplements (2000 mg/day) for 1 month. Arginase activity decreased by 21% in T2DM patients after taking L-citrulline supplements. Additionally, plasma NO levels increased by 38%. There was a modest improvement on H1Ac levels in these patients, though not statistically significant. The effect of L-citrulline on arginase activity was also studied in bovine aortic endothelial cells (BAECs) grown in high glucose (HG) conditions. HG (25 mM, 72 h) caused a 2-fold increase in arginase activity in BAECs and decreased NO production by 30%. L-citrulline (2.5 mM) completely prevented the increase in arginase activity and restored NO production levels. These data indicate that L-citrulline can have therapeutic benefits in diabetic patients through increasing NO levels and thus maintaining vascular function possibly through an arginase inhibition related pathway.

Translation and Psychometric Properties of the Arabic Version of Michigan Neuropathy Screening Instrument in Type 2 Diabetes.

OBJECTIVE: To translate the patient questionnaire section of the Michigan Neuropathy Screening Instrument (MNSI) into Arabic, examine the reliability of the translated version, and provide descriptive data on a sample of patients with type 2 diabetes. METHODS: Researchers used the translation-back translation method to obtain MNSI Arabic. The test was then applied on 76 patients with type 2 diabetes. A subgroup of 25 patients answered MNSI Arabic twice to examine reliability. RESULTS: The intraclass correlation coefficient was 0.87, revealing good reliability of MNSI Arabic. The most common symptoms patients complained of were numbness (62%), prickling feelings (57%), burning pain (47%), and pain with walking (46%). CONCLUSION: Similar to the original MNSI version, our study demonstrates that the Arabic version of the MNSI questionnaire is a reliable tool for screening the symptomatic neuropathy status in patients with type 2 diabetes. Availability of this tool in Arabic will provide valuable and easy-to-obtain screening information regarding diabetic peripheral neuropathy that may help delay its complications by promoting early management.

EFFECT OF AGE AND GENDER ON FASTING AND FOOD-STIMULATED LEVELS OF CALCITONIN, PARATHYROID, AND GASTRIN HORMONES IN HEALTHY ADULTS.

Objective: To investigate the effect of age and gender on basal and food-stimulated serum calcitonin (CT), parathyroid hormone (PTH), and gastrin levels among healthy adults. Methods: Ninety-six healthy adults (76 men and 20 women) aged between 21 and 43 years were recruited. Serum CT, PTH, and gastrin levels were measured after a 9-hour overnight fast, and 1 and 3 hours postprandially. Results: PTH levels decreased early and increased late after feeding. This change was significant in men but not in women. CT levels increased in response to food intake in men but not in women. Gastrin levels were significantly increased after feeding in both men and women. Mean basal and food stimulated CT, PTH, and gastrin levels did not significantly differ between genders. Fasting and post-prandial PTH levels were higher while gastrin levels were lower in older subjects (>30 years old) compared to younger subjects (≤30 years old). Fasting and postprandial CT levels were not significantly different between age groups. Conclusion: Age had a significant effect on fasting and food-stimulated PTH and gastrin hormone levels. The effect of age on PTH levels was independent of baseline vitamin D levels. Men showed significant changes in CT and PTH levels in response to feeding compared to women, although the mean hormone levels were not significantly different between men and women. Abbreviations: CT = calcitonin; MTC = medullary thyroid carcinoma; PTH = parathyroid hormone; SD = standard deviation.

Predetermined Anti-Diabetic Drug Regimen Adjustments during Ramadan Fasting: An Observational Study of Safety.

BACKGROUND: Many Muslim type 2 diabetes mellitus (T2DM) patients choose to fast the month of Ramadan despite the possible adverse health effects brought about by the change in dietary habits, among other things. Clinical data regarding the safety of multi-drug regimens during fasting are particularly scarce. The aim of the study was to evaluate the safety of a drug protocol devised by the authors to accommodate Ramadan's dietary changes, involving dose adjustments of four anti-diabetic drug regimens in T2DM patients fasting Ramadan. METHODS: In this prospective, observational, open-label study, 301 T2DM patients who wished to fast Ramadan were followed during Ramadan and the preceding month. The incidence of hypoglycemia, diabetic ketoacidosis (DKA) and non-ketotic hyperosmolar state (NKHS) was monitored. Patients were classified into four groups: A group (those taking metformin, sulfonylurea and insulin [n=33]); B group (metformin and sulfonylurea [n=89]); C group (metformin and insulin [n=96]); and D group (premixed 70/30, glargine or regular insulin [n=82]). During Ramadan, drug doses were adjusted as percentages of their pre-Ramadan values: 75% for sulfonylureas, 75% for glargine, 75% for premixed insulin 70/30 in two doses, and 75% for regular insulin. Metformin was adjusted to a twice-daily regimen. RESULTS: No cases of DKA or NKHS were reported. Hypoglycemia occurred at a lower rate than pre-Ramadan values in groups C, and D; and a similar rate in groups A, and B. CONCLUSION: The data suggested that using the above protocol to adjust the doses of anti-diabetic drugs is safe in T2DM patients in regards to hypoglycemia, DKA, and NKHS.

SERUM LEVELS OF CARCINOEMBRYONIC ANTIGEN IN PATIENTS WITH TYPE 2 DIABETES.

OBJECTIVE: To investigate whether serum carcinoembryonic antigen (CEA) levels are associated with type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c). METHODS: A comparative, cross-sectional, observational study was conducted at Jordan University Hospital, Amman, Jordan, on 282 adult subjects from March 2012 to June 2015. Subjects were classified into 2 groups: T2DM subjects (n = 168) and a healthy comparison group (n = 114). Subjects with any condition known to be associated with elevated CEA levels were excluded. HbA1c and serum CEA levels were measured, and body mass index (BMI) was determined. RESULTS: Subjects with T2DM had significantly higher mean serum CEA than controls (2.4 ± 1.5 vs. 1.5 ± 1.2 ng/mL, P<.0001). Sex did not correlate with CEA levels, while age (Spearman's rho [ρ] = 0.18, P = .002) and HbA1c (ρ = 0.56, P<.0001) did; however, age no longer correlated after correcting for diabetic status. HbA1c was the only variable shown to correlate with CEA in a stepwise linear regression (r = 0 .37, P<.001). CONCLUSION: We observed a statistically significant association between elevated CEA and T2DM, despite average CEA values for both groups being within the reference range. In addition, serum CEA levels correlated positively with HbA1c values. ABBREVIATIONS: ADA = American Diabetes Association BMI = body mass index CA 19-9 = carbohydrate antigen 19-9 CEA = carcinoembryonic antigen CRP = C-reactive protein DM = diabetes mellitus HbA1c = glycated hemoglobin JUH = Jordan University Hospital T2DM = type 2 diabetes mellitus ρ = Spearman's correlation coefficient.

The prevalence of isolated growth hormone deficiency among children of short stature in Jordan and its relationship with consanguinity.

OBJECTIVE: The prevalence of isolated growth hormone deficiency (IGHD) among short-statured children in Jordan, where consanguineous marriage (CM) is common, is unknown. No studies have investigated the relationship between degrees of consanguinity and IGHD. This study aimed to determine the prevalence of IGHD among short-statured children referred to a university hospital in Jordan and its relationship with different degrees of consanguinity. DESIGN: We conducted a 24-month cross-sectional observational trial at an outpatient tertiary care center in Amman, Jordan. PATIENTS: We obtained detailed family histories, medical evaluations and laboratory tests for 94 short-statured children (50 boys and 44 girls aged 6-16 years). MEASUREMENTS: Complete and partial GHD were defined as peak GH responses of 5 and 7 µg/l (15 and 21 mIU/l) [IRMA/DiaSorin®], respectively, in both exercise and insulin tolerance tests. RESULTS: GHD was diagnosed in 69·1% of the short children, including 86% (43/50) of the children of consanguineous parents (83·3%, 93·8% and 81·8% of children of first cousins, first cousins once removed and second cousins, respectively) and 50% (20/44) of the children of nonconsanguineous parents (P = 0·039, 0·002 and 0·013, respectively). However, there was no statistically significant difference in the prevalence of small pituitary MRI between GH-deficient children of consanguineous parents and those of nonconsanguineous parents (28·6% vs 13·6%, P = 0·3). CONCLUSIONS: The prevalence of IGHD among referred short children in Jordan was exceptionally high and significantly higher in the children of CM. In countries where CM is common, preconception counselling and rigorous surveillance for GHD in short children may be indicated.

Should food intake and circadian rhythm be considered when measuring serum calcitonin level?

OBJECTIVE: To investigate the relationship between both food intake and circadian rhythmicity and serum calcitonin in the same individuals. METHODS: Eighteen healthy subjects, 10 males and 8 females, aged 22 to 24 years, were recruited. Serum calcitonin level was measured three times: at 0800 after a 9-hour overnight fast, at 0900 postprandially, and at 1700 after another 9-hour fast. The same protocol was repeated once. RESULTS: The mean calcitonin levels (at 0800) were 3.92 pg/mL (SD, 2.5 pg/mL) on Day 1 and 3.52 pg/mL (SD, 2.1 pg/mL) on Day 2. Mean postprandial calcitonin (at 0900) was 9.46 pg/mL (SD, 8.6 pg/mL) on Day 1 and 9.91 pg/mL (SD, 6.9 pg/mL) on Day 2. Mean fasting calcitonin in the evening (at 1700) was 6.74 pg/mL (SD, 4.73 pg/mL) on Day 1 and 6.49 pg/mL (SD, 3.57 pg/mL) on Day 2. There was no significant difference in the mean calcitonin level on days 1 and 2 for any of the three time points examined. Statistically significant differences were found between postprandial and evening calcitonin levels and the fasting levels on Day 1 (P = .018 and .015, respectively) and Day 2 (P = .001 and .0009, respectively). CONCLUSION: These results suggest that serum calcitonin level is significantly influenced by food intake in healthy young subjects and reveal a circadian rhythm, with increased calcitonin level during the afternoon. The timing of blood sampling relative to meals should be integrated into clinical practice and research settings involving serum calcitonin measurements.

Study design and baseline characteristics of patients in the PRESENT study.

PRESENT (Physicians' Routine Evaluation of Safety & Efficacy of NovoMix 30 Therapy) is a 6-month observational study of safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in 31,044 type 2 diabetes patients from 15 countries. The aim of this article is to describe the study protocol and assess baseline characteristics of patients in various countries according to diabetes duration (<5 years, 5 to or=20 years), to improve treatment decisions in clinical practice. Glycaemic control was similar across all groups: HbA1c 9.3-9.4%; fasting plasma glucose 11.3-11.6 mmol/L; postprandial glucose 15.9-16.3 mmol/L. Major hypoglycaemia was reported by 5% of all patients, minor hypoglycaemia increased with diabetes duration (25.4-30.3%); overall hypoglycaemia rate was 6.7 events/patient/year. Complications increased with diabetes duration; the most reported were hypertension (40.6-71.0%) and hyperlipidaemia (39.4-56.6%). Of patients 38% previously received OADs only, 28% insulin only, 19% insulin with OADs, and 13% received no therapy. Glycaemic control appeared independent of diabetes duration. HbA1c was well above targets and the clinical inertia was quite apparent; even patients with diabetes for <5 years had high HbA1c levels. Patients suffered high rates of complications and hypoglycaemia before starting BIAsp 30 therapy.

Familial concordance of thyroid and other head and neck tumors in an irradiated cohort: analysis of contributing factors.

Relatively little is known about variations in susceptibility to the effects of radiation in the general population. We have been studying 4296 individuals exposed as children to head and neck radiation. The present study was designed to evaluate the pattern of thyroid, parathyroid, salivary, and neural tumors in irradiated siblings for evidence of heritable susceptibility factors. We also wanted to determine whether the characteristics of thyroid cancers were influenced by familial factors. The following criteria were met by 251 sibling pairs: both irradiated, both with follow-up (average, 44.3 +/- 9.4 yr; range, 9.4-59.5 yr), and both with organ-dose estimates. For each sibling pair we derived a quantitative score, taking into account the length of follow-up and known risk factors, for their concordance and used the sum of these scores to characterize the population. Whether we used thyroid cancer or all thyroid nodules as an end point, the degree of concordance did not exceed what could be explained by the length of follow-up and known risk factors. For thyroid cancer, neither the presenting characteristics nor their rates of recurrence were influenced by their concordance status. In summary, we were unable to identify familial factors that modify the strong effects of radiation exposure. There is no reason to alter the evaluation or treatment of thyroid cancer in an irradiated patient based on whether another member of the family has radiation-related tumors.