Diabetic Female Rats Research Articles

Therapy with methanolic extract of Pterocarpus marsupium Roxb and Ocimum sanctum Linn reverses dyslipidemia and oxidative stress in alloxan induced type I diabetic rat model

Methanolic extracts of Pterocarpus marsupium Roxb (P. marsupium) and Ocimum sanctum Linn (O. sanctum) were prepared separately and then administered to both non-diabetic and alloxan induced diabetic adult female Wistar rats as a mixture of both at a dosage of 500mg/kg body weight, and its effect was checked on serum and tissue lipids together with corticosterone, estrogen and progesterone profile. Further, tissue load of metabolites (cholesterol), enzymatic and non-enzymatic antioxidant status together with lipid peroxidation levels and serum markers of hepatic and renal damage were also assessed. Results of the present study strongly support the possibility of this herbal combination in humans to meet the objective of achieving a holistic amelioration and cure of diabetes as, the herbal extract mixture of P. marsupium and O. sanctum has succeeded in not only rectifying dyslipidemia but also in restoring the endogenous antioxidant levels to the pre diabetic status. Herbal preparations are ideal candidates of choice and in this context, the present combination of P. marsupium and O. sanctum provides compelling evidence for a holistic efficacy in amelioration of associated diabetic manifestations/dysregulations.

Impact of opium on the serum levels of TGF-β in diabetic, addicted and addicted-diabetic rats.

Several cells of immune system such as regulatory T cells and macrophages secrete transforming growth factor-β (TGF-β) in response to different stimuli. This cytokine has inhibitory effect on immune system and diminished production of this cytokine is associated with autoimmune disorders. The aim of this study was to evaluate the influence of opium addiction on serum level of TGF-β in male and female diabetic and non-diabetic Wistar rats. This experimental study was performed on normal, opium addicted, diabetic and addicted-diabetic male and female rats. Serum level of TGF-β was measured by ELISA. The results of our study indicated that the mean serum level of TGF-β in female addicted rats was significantly increased compared to control group (p<0.004). Conversely, in male addicted rats the mean serum level of TGF-β was lower compared with control (p<0.065). Our results suggest that opium and its derivatives have differential inductive effects on the cytokine expression in male and female rats.

Sepiapterin reverses the changes in gastric nNOS dimerization and function in diabetic gastroparesis

We have demonstrated previously that in vivo supplementation of tetrahydrobiopterin (BH₄); a co-factor for neuronal nitric oxide synthase (nNOS) significantly restored delayed gastric emptying and attenuated nitrergic relaxation in diabetic rat. In this study, we have investigated whether supplementation of sepiapterin (SEP), a precursor for BH₄ biosynthesis via salvage pathway restores gastric emptying and nitrergic system in female diabetic rats. Diabetic rats (streptozotocin-induced) were supplemented with BH₄ or SEP (20 mg kg⁻¹ body weight). Gastric nitrergic relaxation in the presence or absence of high glucose and SEP were measured by electric field stimulation. Gastric muscular strips from healthy or diabetic female rats were incubated in the presence or absence of high glucose, SEP and/or methotrexate (MTX). Nitric oxide release was measured colorimetrically by NO assay kit. The expression of nNOSα and dimerization was detected by Western blot. In vitro studies on gastric muscular tissues showed that MTX, an inhibitor of BH₄ synthesis via salvage pathway, significantly decreased NO release. In vivo treatment with MTX reduced both gastric nitrergic relaxation and nNOSα dimerization. Supplementation of SEP significantly attenuated delayed gastric emptying in diabetic rats. In addition, SEP supplementation restored impaired nitrergic relaxation, gastric nNOSα protein expression, and dimerization in diabetic rats. The above data suggests that supplementation of SEP accelerated gastric emptying and attenuated reduced gastric nNOSα expression, and dimerization. Therefore, SEP supplementation is a potential therapeutic option for female patients of diabetic gastroparesis.

Role of insulin on jejunal PepT1 expression and function regulation in diabetic male and female rats

The aim of this study was to determine whether the jejunal oligopeptide transporter PepT1 is regulated by insulin and whether this regulation is sex-dependent in type 1 diabetic rats. PepT1 expression, real-time polymerase chain reaction, and Western blots were performed using jejunal segments from 4 groups of male and female rats: normal (nondiabetic), insulin-treated nondiabetic, streptozotocin (STZ)-induced diabetic (type 1 diabetes), and insulin-treated diabetic models. Furthermore, the same segments from all groups underwent perfusion to assess uptake of the dipeptide glycylsarcosine through PepT1. Our results showed that insulin treatment of nondiabetic female rats decreased blood glucose level but did not affect nondiabetic male rats. In both male and female diabetic rats, insulin did not completely decrease blood glucose level. Insulin treatment decreased PepT1 mRNA level in nondiabetic male rats and increased mRNA level in nondiabetic female rats without affecting the PepT1 protein level in either sex. Inducing diabetes with STZ increased PepT1 mRNA and protein levels in female rats; however, in diabetic male rats, the increase in mRNA level was accompanied by a decrease in PepT1 protein level. Treatment of diabetic male rats with insulin partially reversed the effect of diabetes on PepT1 mRNA and protein levels, whereas the same treatment completely restored both PepT1 mRNA and protein to control levels in insulin-treated diabetic female rats. In both nondiabetic male and female rats, insulin treatment had no effect on PepT1 influx rate, and STZ treatment decreased the transporter influx rate. Treatment of diabetic male and female rats with insulin significantly increased PepT1 influx rate; however, complete recovery was found only in diabetic female rats. These results clearly show that insulin and diabetes affected blood glucose level as well as PepT1 activity, expression, and protein levels in a sex-dependent manner. These results suggest that a factor, probably estrogen, could be responsible for the sex-dependent effects of diabetes and insulin in PepT1 level and activity.

Potential of Hydroalcoholic Extract of Tylophora indica Leaves for Antidiabetic Property in Rat

The present study was carried out to ascertain the role of hydroalcoholic extract of Tylophora indica leaves for its possible antidiabetic potentials in streptozotocin (STZ) induced diabetic Wistar female rats. A single intraperitoneal injection of STZ (55 mg/kg) elevated the glucose level>230 mg/dl after 3 days. Oral administration of the hydroalcoholic extract of Tylophora indica leaves at 100 and 250 mg/kg resulted in significant reduction (P<0.001) in blood glucose level. Body weight was significantly reduced (P<0.001) in STZ induced diabetic rats when compared to normal rats, while in diabetic rats Tylophora indica leaves extract (P<0.001) prevented significantly the decrease in body weight in a dose dependant manner. Total cholesterol, triglyceride, LDL-c and HDL-c levels were altered in STZ induced diabetic rats, which were considerably restored to near normal in animals treated with Tylophora indica extract. The administration of hydroalcoholic extract of Tylophora indica resulted in significant (P<0.001) increase in the levels of superoxide dismutase, catalase, glutahione peroxidase, glutathione-S-transferase and reduced glutathione, thus resulting in reduced free radical formation in liver tissues of the diabetic rat. These observations demonstrated the dose dependent antidiabetic effect of hydroalcoholic extract of Tylophora indica leaves in STZ-induced diabetic rat.

M2007 Supplementation of Tetrahydrobiopterin (BH4) Improves Nitric Oxide (NO) Down Stream Signaling Mediated Gastric Pyloric Smooth Muscle Relaxation in Female Diabetic Rats

M2007 Supplementation of Tetrahydrobiopterin (BH4) Improves Nitric Oxide (NO) Down Stream Signaling Mediated Gastric Pyloric Smooth Muscle Relaxation in Female Diabetic Rats

Tetrahydrobiopterin (BH4), a cofactor for nNOS, restores gastric emptying and nNOS expression in female diabetic rats

Gastroparesis is a debilitating disease predominantly affecting young women. Recently, dysregulation of neuronal nitric oxide synthase (nNOS) in myenteric plexus neurons has been implicated for delayed solid gastric emptying/gastroparesis in diabetic patients. In this study, we have explored the role of tetrahydrobiopterin (BH4), a major cofactor for nNOS activity and NO synthesis in diabetic gastroparesis. Diabetes was induced with single injection of streptozotocin (55 mg/kg body wt, ip) in female rats, with experiments performed on week 3 or 9 following induction, with or without 3-wk BH4 supplementation. Gastric pyloric BH4 levels were significantly decreased in diabetic female rats compared with control (18.6 +/- 1.45 vs. 31.0 +/- 2.31 pmol/mg protein). In vitro studies showed that 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of BH4 synthesis, significantly decreased gastric NO release and nitrergic relaxation. Three-week dietary supplementation of BH4 either from day 1 or week 6 significantly attenuated diabetes-induced delayed gastric emptying for solids (3 wk: BH4, 67 +/- 6.7 vs. diabetic, 36.05 +/- 7.09; 9 wk: BH4, 57 +/- 8.45 vs. diabetic, 33 +/- 9.91) and diabetes-induced reduction in pyloric nNOS-alpha protein expression in female rats. Supplementation of BH4 significantly restored gastric nNOS-alpha dimerization in 9-wk-old diabetic female rats. In addition, BH4 treatment reversed (17.23 +/- 5.81 vs. 42.0 +/- 2.70 mmHg x s) the diabetes-induced changes in intragastric pressures (IGP) and gastric pyloric nitrergic relaxation (-0.62 +/- 0.01 vs. -0.22 +/- 0.07). BH4 deficiency plays a critical role in diabetes-induced alterations including delayed solid gastric emptying, increased IGP, reduced pyloric nitrergic relaxation, and nNOS-alpha expression in female rats. Supplementation of BH4 accelerates gastric emptying by restoring nitrergic system in diabetic female rats. Therefore, BH4 supplementation is a potential therapeutic option for female patients of diabetic gastroparesis.

Effect of estrogen on electroretinographic responses in streptozotocin-induced diabetic female rats

The aim of this study is to investigate the effects of estrogen on functional changes in the retinas of streptozotocin (STZ)-induced diabetic rats by using an electroretinography. Female rats were randomly divided into four treatment groups: (1) Control (sham operation and vehicle administration); (2) STZ (sham operation and STZ administration); (3) OVX (ovariectomy and vehicle administration); and (4) OVX + STZ (ovariectomy and STZ administration). Full-field electroretinograms (ERGs) were recorded before OVX and STZ administration and 4 and 12 weeks after STZ administration. At 4 weeks after STZ administration, although there were no differences in the STZ and OVX groups compared with the Control group, the amplitude of the cone-response was significantly lower in the OVX + STZ group than in the Control group (P = 0.013). At 12 weeks after STZ administration, this response showed a similar tendency in the STZ and the OVX + STZ groups. At 12 weeks after STZ administration, the implicit times of OP3 and OP4 and of the cone-response were significantly delayed in the STZ and OVX + STZ groups (OP3: P = 0.030 and 0.050, OP4: P = 0.0060 and 0.0053, cone-response: P = 0.014 and 0.039), compared with in the Control group. Thus, the retinal functions in STZ-induced diabetic female rats were aggravated by OVX. OVX-induced estrogen deficiency resulted in earlier changes in the amplitudes of cone-response, especially in the diabetes, although this is a transient effect and it is difficult to explain. Recognizing the early neurosensory change would enable a better understanding of the effect of estrogen in the retina.

Catalase activity, lipid peroxidation, cholesterol and triglyceride levels in alloxan – induced diabetes mellitus in female and male rats.

Diabetes mellitus is a disorder of carbohydrate metabolism and is associated with oxidative reactions. The present study is to determine the activities of catalase, lipid peroxidation, glucose, protein, cholesterol and triglyceride concentrations in the liver and kidney in alloxan-induced diabetes in female and male rats. In addition, the study is to ascertain if gender differences affect oxidative stress in diabetes. Forty male (165 +/- 8.46 g) and female (162.7 +/- 7.94 g) albino Sprague Dawley rats were used for the study. The rats were injected intraperitoneally with a single dose of 150 mg/body weight of alloxan monohydrate, to induce diabetes-for 14 days. The rats were divided into four groups, consisting of 10 diabetic male, 10 non-diabetic male, 10 diabetic female and 10 non-diabetic female. The rats were fed rat chow and water ad libitum for 14 days and then sacrificed by decapitation. Blood was taken by cardiac puncture, while liver and kidney were quickly excised. The catalase activity, lipid peroxidation, glucose, protein, cholesterol and triglyceride concentrations in the liver and kidney of rats were determined. Bats administered alloxan monohydrate had elevated plasma glucose levels. The body weights of diabetic female and male rats were significantly reduced compared to the non-diabetic rats. The catalase activities in liver and kidney of diabetic male or female rats were significantly lower than in non-diabetic rats but the reduction was more pronounced in diabetic female rats. The liver lipid peroxidation, cholesterol and triglyceride levels were significantly higher in the diabetic male or female than in the non-diabetic rats, but with no significant differences in the diabetic female or male rats. Data of the study indicate that sex differences do not significantly affect oxidative stress in alloxan-induced diabetes mellitus.

Improvement of Hyperglycemia and Sexual Dysfunction in Diabetic Female Rats by an Artificial Endocrine Pancreas Developed from Mouse .BETA. Cells

We investigated the effects of a bioartificial endocrine pancreas (Bio-AEP) produced by mouse beta cells on sexual dysfunction of streptozotocin (STZ)-induced diabetic female rats. Female rats were administered STZ (60 mg/kg BW, i.v.) at the age of 10 weeks and transplanted with a Bio-AEP including mouse beta cells at the age of 14 weeks (STZ+Bio-AEP group). Lordosis and proceptive sexual behavior of female rats were observed. The results showed that after the Bio-AEP transplant blood glucose recovered from 380-450 mg/dl induced by streptozotocin to 140-230 mg/dl and suppressed lordosis and proceptive behavior also recovered. These results suggest that it is possible to reverse sexual dysfunction by continuous administration of mouse insulin.

Voiding function in obese and type 2 diabetic female rats

The effects of obesity and type 2 diabetes (DMII) on the lower urinary tract (LUT) were characterized by evaluating voiding function and anatomy in female Zucker diabetic fatty (ZDF) rats. Age-matched female virgin rats were separated into three experimental groups: Zucker lean rats (control; normal diet, n = 22), ZDF rats (obese+nondiabetic; low-fat diet, n = 22), and ZDF rats (obese+diabetic; high-fat diet, n = 20). Rats were placed on their specified diet for 10 wk before urodynamic LUT evaluation. A suprapubic catheter was implanted 2 days before urodynamic studies. Voiding function was evaluated by cystometric and leak point pressure (LPP) testing. The bladder, urethra, and vagina were immediately excised for qualitative histological evaluation. Compared with control rats, obese+nondiabetic and obese+diabetic rats had significantly decreased contraction pressure (P = 0.003) and increased cystometric filling volume (P < 0.001). Both obese groups exhibited significantly higher voided volumes (P = 0.003), less frequent urinary events (P < 0.001), and increased residual volumes (P = 0.039). LPP studies showed a nonsignificant decrease in LPP (P = 0.075) and baseline pressure (P = 0.168) in both obese groups compared with control. Histology of the external urethral sphincter in obese rats showed increased fibrosis, leading to disruption of the skeletal muscle structure compared with control. Additionally, the bladder wall of the obese+nondiabetic and obese+diabetic rats demonstrated edema and vasculopathy. Voiding dysfunction was evident in both obese groups but with no significant differences due to DMII, suggesting that voiding dysfunction in DMII may be attributable at least in part to chronic obesity.

Diabetes alters aromatase enzyme levels in sciatic nerve and hippocampus tissues of rats.

Diabetes mellitus (DM) is associated with increased risk of impaired cognitive function. Diabetic neuropathy is one of the most common and important complications of DM. Estrogens prevent neuronal loss in experimental models of neurodegeneration and accelerate nerve regeneration. Aromatase catalyzes the conversion of androgens to estrogens and expressed in a variety of tissues including neurons. Although insulin is known to regulate the activity of aromatase there is no study about the effects of diabetes on this enzyme. Present study was designed to investigate the effects of experimental diabetes on aromatase expression in nervous system. Gender-based differences were also investigated. Rats were injected with streptozotocin to induce diabetes. At the end of 4 and 12 weeks sciatic nerve and hippocampus homogenates were prepared and evaluated for aromatase proteins. Aromatase expressions in sciatic nerves of both genders were decreased in 4 weeks of diabetes, but in 12 weeks the enzyme levels were increased in females and reached to control levels in male animals. Aromatase levels were not altered in hippocampus at 4 weeks but increased at 12 weeks in female diabetic rats. No significant differences were observed at enzyme levels of hippocampus in male diabetic rats. Insulin therapy prevented all diabetes-induced changes. In conclusion, these results indicated for the first time that, DM altered the expression of aromatase both in central and peripheral nervous systems. Peripheral nervous system is more vulnerable to damage than central nervous system in diabetes. These effects of diabetes differ with gender and compensatory neuroprotective mechanisms are more efficient in female rats.

Sex differences in neuroactive steroid levels in the nervous system of diabetic and non-diabetic rats

Neuropathy and encephalopathy represent important complications of diabetes. Recent observations obtained in experimental models have suggested that, in male rats, neuroactive steroids are protective agents and that their levels in peripheral (PNS) and central (CNS) nervous system are strongly affected by the disease. It is interesting to highlight that incidence, progression and severity of diabetic neuropathy and diabetic encephalopathy are different in the two sexes. Consequently, it is important to determine the changes in neuroactive steroid levels in the PNS and the CNS of both males and females. To this aim, we have evaluated the levels of neuroactive steroids such as, pregnenolone, progesterone and its metabolites, testosterone and its metabolites, and dehydroepiandrosterone in different CNS regions (i.e., cerebral cortex, cerebellum and spinal cord) and in the sciatic nerve of control and diabetic (i.e., induced by streptozotocin) male and female rats. Data obtained by liquid chromatography–tandem mass spectrometry indicate that the levels of neuroactive steroids show sex and regional differences in control animals. Streptozotocin-induced diabetes resulted in a strong general decrease in neuroactive steroid levels, in both the PNS and the CNS. In addition, the effects of diabetes on neuroactive steroid levels also show sex and regional differences. These findings may have strong implications for the development of new sex-oriented therapies for the treatment of diabetic neuropathy and diabetic encephalopathy, based on the use of neuroactive steroids.

W2056 Sepiapterin, a Precursor for Tetrahydrobiopterin (Bh4, a Cofactor for nNOS Activity), Restores Gastric Emptying and nNOS Alpha Protein Expression in Female Diabetic Rats

W2056 Sepiapterin, a Precursor for Tetrahydrobiopterin (Bh4, a Cofactor for nNOS Activity), Restores Gastric Emptying and nNOS Alpha Protein Expression in Female Diabetic Rats

Antihyperglycemic, Hypolipidemic and Antioxidant Enzymes Effect of Strobilanthes crispus Juice in Normal and Streptozotocin-Induced Diabetic Male and Female Rats

The aim of the present study was to investigate the effect of Strobilanthes crispus juice on glucose, lipid profile, glutathione peroxidase and superoxide dismutase in normal and streptozotocin-induced diabetic male and female albino Sprague-Dawley rats. This study was conducted on normal and streptozotocin-induced diabetic male and female Sprague-Dawley rats fed with basal diet and S. crispus juice with different doses 1.0, 1.5 and 2.0 mL k-1 b.wt. for 30 days. The results showed that significant (p<0.05) decrease in serum glucose levels in male and female diabetic and normal rats with treated S. crispus juice (1.0, 1.5 and 2.0 mL k-1 b.wt.). Cholesterol and triglyceride level significantly (p<0.05) decreased in diabetic rats treated with 1.0, 1.5 and 2.0 mL k-1 b.wt. of S. crispus juice. Cholesterol, triglyceride and LDL-cholesterol level showed reduction in treated male and female normal rats. HDL-cholesterol showed the increasing but not significant (p<0.05) difference in treated diabetic and normal male and female rats. Glutathione peroxidase and superoxide dismutase activities significantly (p<0.05) increased in treated diabetic and normal male and female rats. In conclusion, S. crispus juice possesses antihyperglycemic, hypolipidemic and antioxidant effect in streptozotocin-induced diabetic rats. Thus, S. crispus juice could be the alternative treatment for lowering glucose, cholesterol and triglyceride for diabetic patients in the future.

Effect of experimental diabetes on the development and maintenance of vulvovaginal candidiasis in female rats

The purpose of this study was to develop an experimental model of diabetes in female rats and verify its influence on vulvovaginal candidiasis. The animals were divided into control and diabetic groups. Diabetes was induced with the use of an intravenous solution of alloxan (42 mg/kg bodyweight). One week after confirmation of hyperglycemia, the inoculation of Candida albicans yeast, previously standardized from a vaginal isolate, in concentrations of about 5 x 10(8), was performed. Infection control was made through vaginal culture, Papanicolaou cytology, and scanning electron microscopy (SCEM). The results pointed to different glycemias between the control (74.8 +/- 2.6) and experimental groups (543.1 +/- 12.1) and a significant bodyweight decrease (227.6 +/- 4.77 and 204 +/- 6.39, respectively). The positive infection was shown by culture, Papanicolaou test, and SCEM in the experimental group. Diabetes mellitus causes hyperglycemia, which was favorable to the vaginal colonization and infection by C albicans.

The Response of Creatine Kinase Specific Activity in Rat Pituitary to Estrogenic Compounds and Vitamin D Less-Calcemic Analogs

We examined the response of rat female pituitary at different metabolic stages to treatments with estrogenic compounds and vitamin D analogs. Immature or ovariectomized (Ovx) female rats responded by increased creatine kinase specific activity (CK) to estradiol-17β (E2), genistein (G), daidzein (D), biochainin A (BA), quecertin (Qu), carboxy- G (cG), carboxy- BA (cBA), and raloxifene (Ral). The response was inhibited when Ral was injected together with the estrogens. CK was increased when hormones were injected daily into Ovx rats for 4 different time periods. Pretreatment with the less-calcemic vitamin D analogs JK 1624 F2-2 (JKF) or QW 1624 F2-2 (QW) followed by estrogenic injection resulted in increased response and sensitivity to E2 and loss of inhibition of E2 by Ral. CK was also increased by feeding with E2 or licorice or its components dose- and time- dependent in immature or Ovxrats. Diabetic female rats did not respond to increased doses of E2. In conclusion, rat female pituitary is estrogens-responsive organ, suggesting to considerits response for HRT in postmenopausal women for both beneficial and hazardous aspects.

Acute diabetes mellitus and its influence on renal Na,K-ATPase in both genders

Due to the importance of renal Na,K-ATPase in maintaining the sodium homeostasis in the organism, its activity and abundance is intensively studied in condition of diabetes mellitus. The main subject of this study was the investigation of properties of renal Na,K-ATPase and abundance of its alpha1 subunit in view of possible gender-dependent differences in male and female diabetic rats. Diabetes was induced by a single intraperitoneal dose of streptozotocin in a dose of 65 mg.kg(-1). The acute diabetes lasting 8 days induced a significant increase in Na,K-ATPase activity accompanied by significant gender specific increase in K(m) value indicating a worsened affinity of ATP-binding site in female rats. In addition, our present experiments, revealed a significantly higher abundance of renal Na,K-ATPase alpha1 subunit in diabetic rats of both genders amounting 94% increase in males and 107% in females. But, not all of the newly synthesized enzyme molecules are fully active, as the increase in the number of active molecules is smaller (representing 23% in males and 20% in females) as indicated by lower increase in V(max) values.

The levels of vascular endothelial growth factor-A and placental growth factor-2 in embryopathy associated with experimental diabetic gestation

The objective of this study was to investigate the role of vascular endothelial growth factor-A (VEGF-A) and placental growth factor-2 (PlGF-2) in fetal malformations associated with maternal diabetes. Diabetes was induced in female rats. Diabetic and control female rats were made pregnant. On Day 15 of gestation, rats were sacrificed and embryos and their placentas and membranes were dissected out of the uterine horns. Following morphological examination, embryos and their placentas and membranes were homogenized and used for assayed of VEGF-A and PlGF-2 levels. Embryos of diabetic mothers, exhibited significantly (P < 0.05) shorter crown-to-rump lengths, smaller weights, and heavier placental weights. Experimentally induced maternal diabetes was accompanied by decreased VEGF-A in embryos and associated structures. The levels of PlGF-2 in non-malformed embryos of diabetic gestation and their placentas were significantly (P < 0.05) lower than the average of controls. These results might indicate defective vascularization with a consequent morphological or anatomical anomalies or more subtle biochemical or metabolic changes. In diabetic mothers, a statistically significant (P < 0.05) decrease was noted in the level of VEGF-A in plasma of diabetic rats with a small non-significant decrease in PlGF-2. Like many other diabetic complications, diabetes-induced embryopathies might have vascular origin and correcting the disturbances in these angiogenic factors might help decrease the incidence of malformation in diabetic gestation

Type 2 Diabetes Mellitus and Risk of Stress, Urge and Mixed Urinary Incontinence

To improve the understanding of the etiological relation between type 2 diabetes and urinary incontinence, we examined associations between diabetes and urinary incontinence type in 71,650 women 37 to 79 years old in the Nurses' Health Study and the Nurses' Health Study II. From 1976 to 2000 in the Nurses' Health Study and 1989 to 2001 in the Nurses' Health Study II participants reported diagnoses of type 2 diabetes. Women with incident urinary incontinence at least weekly were identified from 2000 to 2002 in the Nurses' Health Study and 2001 to 2003 in the Nurses' Health Study II. We pooled data from the 2 cohorts, and estimated odds ratios and 95% confidence intervals using multivariable logistic regression adjusting for age, parity, body mass index, smoking, hysterectomy, functional limitations, menopausal status, postmenopausal hormone use, incontinence promoting medications and study cohort. The incidence of at least weekly urinary incontinence was 5.3% (3,612 of 67,984) among women without type 2 diabetes and 8.7% (318 of 3,666) among women with diabetes. Overall the multivariable adjusted odds of incident urinary incontinence were increased 20% (OR 1.2, 95% CI 1.0-1.3, p = 0.01) among women with vs without type 2 diabetes. This increase appeared largely explained by significantly greater odds of urge urinary incontinence (OR 1.4, 95% CI 1.0-1.9, p = 0.03). There was no apparent association between diabetes and stress (p = 0.3) or mixed (p = 0.6) urinary incontinence, although confidence intervals were somewhat wide. Our findings suggest that type 2 diabetes may especially influence urge urinary incontinence. Further research is needed to confirm this finding and identify pathways linking these conditions.