Reactive arthritis in a population exposed to an extensive waterborne gastroenteritis outbreak after sewage contamination in Pirkanmaa, Finland.

OBJECTIVES: To assess the occurrence, clinical picture, and triggering infections of reactive arthritis (ReA) associated with a large waterborne gastroenteritis outbreak. METHODS: After an extensive sewage contamination of the water supply system, an estimated 8453 of the 30 016 inhabitants of the town of Nokia fell ill. General practitioners and occupational physicians were advised to refer any patients with suspicion of new ReA to rheumatological examination including faecal culture, human leucocyte antigen (HLA)-B27 and antibody tests for Campylobacter, Salmonella, and Yersinia. RESULTS: Forty-five patients (33 females, 12 males) aged 16-77 years (median 53) were referred. ReA was diagnosed in 21, postinfectious arthralgia in 13, and other musculoskeletal conditions in 11 patients. HLA-B27 was positive in five out of 44 patients (11%). Of the 21 patients with ReA, possible triggering infections were observed in seven (33%), Campylobacter in four, Yersinia in three, and Salmonella in one, who also had Campylobacter infection. ReA was mild in all but one patient who presented with persistent Salmonella enterica serotype enteritidis infection. CONCLUSIONS: Taking into account the large population contaminated with potentially arthritogenic agents, the occurrence of ReA was rare and mild in character.

An extensive gastroenteritis outbreak after drinking-water contamination by sewage effluent, Finland.

An inappropriate cross-connection between sewage- and drinking-water pipelines contaminated tap water in a Finnish town, resulting in an extensive waterborne gastroenteritis outbreak in this developed country. According to a database and a line-list, altogether 1222 subjects sought medical care as a result of this exposure. Seven pathogens were found in patient samples of those who sought treatment. To establish the true disease burden from this exposure, we undertook a population-based questionnaire investigation with a control population, infrequently used to study waterborne outbreaks. The study covered three areas, contaminated and uncontaminated parts of the town and a control town. An estimated 8453 residents fell ill during the outbreak, the excess number of illnesses being 6501. Attack rates were 53% [95% confidence interval (CI) 49.5-56.4] in the contaminated area, 15.6% (95% CI 13.1-18.5) in the uncontaminated area and 6.5% (95% CI 4.8-8.8) in the control population. Using a control population allowed us to differentiate baseline morbidity from the observed morbidity caused by the water contamination, thus enabling a more accurate estimate of the disease burden of this outbreak.

Diagnosis and treatment of menorrhagia.

One-third of all women experience heavy menstrual bleeding at some point in their life. In western countries, about 5% of women of reproductive age will seek help for menorrhagia annually. Half of all women who consult for hypermenorrhea have some uterine abnormality, most often fibroids (among patients under 40 years of age) and endometrial polyps (above 40 years of age). Appropriate treatment considerably improves the quality of life of these patients, and it is important to make a rigorous assessment of the patient to provide the best treatment options. This guideline provides instructions on how to examine and treat women of fertile age who have menorrhagia. The subject's own assessment of the amount of menstrual blood loss does not generally reflect the true amount. All patients should undergo a pelvic examination and, if the menstrual pattern has changed substantially or if anaemia is present, a vaginal sonography should be carried out as the most important supplemental examination. Vaginal sonography combined with an endometrial biopsy is a reliable method for diagnosing endometrial hyperplasia or carcinoma, but it is insufficient for diagnosing endometrial polyps and fibroids; these can be diagnosed more reliably by sonohysterography or hysteroscopy. Non-steroidal anti-inflammatory drugs and tranexamic acid reduce menstrual blood loss by 20-60%, and the effectiveness of a hormonal intrauterine system (IUS) is comparable with that of endometrial ablation or hysterectomy. Cyclic progestogens do not significantly reduce menstrual bleeding of women who ovulate. Treatment should be started with one of the drug therapies, i.e. the IUS, tranexamic acid, anti-inflammatory drugs, or oral contraceptive. Drug treatment should be used and evaluated before surgical interventions are considered. With an effective training and feedback system, it is possible to organise the diagnostics, medical treatment and follow-up of heavy menstrual bleeding in the primary health care setting or in outpatient clinics, which reduces the burden on specialist health care.

The effect of hysterectomy or levonorgestrel-releasing intrauterine system on sexual functioning among women with menorrhagia: a 5-year randomised controlled trial.

OBJECTIVE: To compare among women with menorrhagia the effect of hysterectomy or levonorgestrel-releasing intrauterine system (LNG-IUS) on sexual functioning. DESIGN: A randomised controlled trial. SETTING: Five university hospitals in Finland. SAMPLE: A total of 236 women, aged 35-49 years. METHODS: Of the women, 117 were treated by hysterectomy and 119 by LNG-IUS. MAIN OUTCOME MEASURES: Sexual functioning was evaluated by modified McCoy sexual scale at baseline and at 6 months, 12 months, and 5 years after initiation of treatment (hysterectomy or application of LNG-IUS). RESULTS: Among women treated by hysterectomy, sexual satisfaction increased and sexual problems decreased. Among LNG-IUS users, satisfaction with partner decreased. In addition to treatment modality (P = 0.02), estrogen therapy (P = 0.01), smoking (P = 0.001), night sweats (P = 0.03), vaginal dryness (P = 0.04), hot flushes (P = 0.01), and having someone to ask for advice (P = 0.03) and to share worries (P = 0.01) explained changes in sexual functioning. CONCLUSIONS: Among women with menorrhagia, hysterectomy improves sexual functioning, whereas LNG-IUS does not have such a positive effect.

A randomized controlled trial of hysterectomy or levonorgestrel-releasing intrauterine system in the treatment of menorrhagia-effect on FSH levels and menopausal symptoms.

BACKGROUND: The purpose of this study was to compare the effects of hysterectomy and a levonorgestrel-releasing intrauterine system (LNG-IUS) on serum FSH levels and menopausal symptoms. METHODS: A total of 236 women referred for menorrhagia to five university hospitals were randomly assigned to treatment with hysterectomy (n = 117) or LNG-IUS (n = 119). Menopausal symptoms were characterized by the Kupperman menopausal distress test. Serum FSH and estradiol levels were measured at baseline and 6 and 12 months after hysterectomy or application of LNG-IUS. Analyses were by intention to treat. RESULTS: After 6 months, there was no difference between the groups, but 12 months after follow-up hysterectomized women had higher FSH levels than women with LNG-IUS (P = 0.005). There was a significant association between FSH levels and treatment modality (P = 0.020). Hot flushes increased significantly in the hysterectomy group (P = 0.02). There was a significant association between hot flushes and both treatment modality and age (P = 0.02 and P = 0.01, respectively). CONCLUSION: Hysterectomy may impair ovarian function shown by rising serum FSH levels and hot flushes. However, these results should be interpreted with caution, and longer follow-up is needed.

Comparison of ovarian cyst formation in women using the levonorgestrel-releasing intrauterine system vs. hysterectomy.

OBJECTIVE: To analyze the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) on ovarian cyst formation, endometrial thickness and the size of uterus and uterine fibroids by ultrasonography. SUBJECTS AND METHODS: This was a prospective, randomized trial comparing the LNG-IUS and hysterectomy in 236 women (age range 35-49 years) referred for menorrhagia. Transvaginal ultrasound examination was used to study the presence of ovarian cysts, uterine size, endometrial thickness, and the size of the uterus and uterine fibroids during a 12-month follow-up period. RESULTS: At baseline examination, 12 ovarian cysts were detected, eight in the LNG-IUS group and four in the hysterectomy group. During the follow-up period, 14 new cysts had emerged at 6 months and 14 new cysts had emerged at 12 months in the LNG-IUS group, whereas the corresponding figures in the hysterectomy group were three and eight, respectively. All but one of the 14 new cysts (94.1%) detected at 6 months in the LNG-IUS group resolved spontaneously, whereas two out of the eight cysts detected at the baseline examination persisted for 12 months. Three cysts were removed at operation. The relative risk of the occurrence of ovarian cysts was significantly higher in women with LNG-IUS, compared with women who underwent hysterectomy. LNG-IUS did not affect the size of the uterus or uterine fibroids, but it was associated with a decrease in endometrial thickness. The occurrence of cysts did not correlate with age or follicle stimulating hormone levels, but a weak positive correlation between the occurrence of cysts and the presence of irregular bleeding was observed. CONCLUSIONS: LNG-IUS use in the treatment of menorrhagia was associated with the development of ovarian cysts, but these were symptomless and showed a high rate of spontaneous resolution. LNG-IUS did not affect the size of the uterus or the size of uterine fibroids, but decreased the thickness of the endometrium.

Laparoscopically assisted vaginal and abdominal hysterectomy: comparison of postoperative pain, fatigue and systemic response. A case-control study.

BACKGROUND AND OBJECTIVE: Laparoscopic and open surgery have been compared with conflicting results regarding their systemic responses. The sensitivity of biochemical markers that are used to discriminate between the stress responses to different types of surgery varies from study to study. We wanted to evaluate the stress response and the sensitivity of clinical and biochemical stress markers in patients undergoing laparoscopically assisted vaginal or abdominal hysterectomy. METHODS: We performed a case-control study with patients undergoing laparoscopically assisted vaginal hysterectomy (n=20) or abdominal hysterectomy (n=20). Pain scores were assessed at rest and during coughing, and active leg elevation and fatigue scores using a visual analogue scale. In 10 patients of each group, haematocrit, white cell count, C-reactive protein, glucose, cortisol, adrenocorticotrophic hormone, beta-endorphin immunoreactivity, interleukin-6 and urine excretion of epinephrine and norepinephrine were measured preoperatively and during the first 44 postoperative hours. RESULTS: The most sensitive symptoms and markers of the systemic response were pain scores during mobilization, fatigue scores, C-reactive protein and interleukin-6 (P < 0.01 in all comparisons). Pain scores at rest, and all other laboratory markers of the systemic response, did not discriminate between the two types of surgery. CONCLUSION: Follow-up of postoperative pain scores during mobilization and fatigue levels might be an easy tool for the evaluation of postoperative recovery. Using an identical anaesthetic technique, the neuroendocrine response was of the same magnitude after both types of surgery.

Psychosocial and other characteristics of women complaining of menorrhagia, with and without actual increased menstrual blood loss.

OBJECTIVE: To discover whether psychosocial factors can explain why many women with normal menstrual blood loss seek care for menorrhagia. DESIGN: Cross-sectional comparative study of women referred for menorrhagia. SETTING: Gynaecology departments of all five university teaching hospitals in Finland. SAMPLE: Two hundred and twenty-six women aged 35-49 years complaining of menorrhagia. MAIN OUTCOME MEASURES: Several psychosocial factors, seeking medical attention, menstrual blood loss. RESULTS: Twenty-nine percent of the women had their menstrual blood loss in the normal range (menstrual blood loss <60 mL). By univariate analysis, unemployment, anxiety, perceived inconvenience, abdominal pain, haemoglobin level and serum ferritin concentration distinguished this group of women from those with true menorrhagia. Unemployment, perceived inconvenience, abdominal pain and serum ferritin remained significant variables by multivariate analysis. CONCLUSIONS: A significant proportion of women with complaints of menorrhagia have their measured menstrual blood loss within the normal range. Psychosocial factors can have an impact on their seeking health care. Better understanding of the factors, which explain complaints of menorrhagia in women with normal bleeding could improve both medical outcomes and reduce the cost of treatment for menorrhagia.

Quality of life and cost-effectiveness of levonorgestrel-releasing intrauterine system versus hysterectomy for treatment of menorrhagia: a randomised trial.

BACKGROUND: Heavy menstrual blood loss is a common reason for women to seek medical care. The levonorgestrel-releasing intrauterine system (IUS) is an effective medical treatment for menorrhagia. We report a randomised comparison of this approach with hysterectomy in terms of the quality of life of women with menorrhagia and cost-effectiveness. METHODS: Of 598 women referred with menorrhagia to five university hospitals in Finland, 236 were eligible and agreed to take part. They were randomly assigned treatment with the levonorgestrel-releasing IUS (n=119) or hysterectomy (n=117). The amount of menstrual blood loss was objectively measured. The primary outcome measure was health-related quality of life at 12-month follow-up. Analyses were by intention to treat. FINDINGS: In the group assigned the levonorgestrel-releasing IUS, 24 (20%) women had had hysterectomy and 81 (68%) continued to use the system at 12 months. Of the women assigned to the hysterectomy group, 107 underwent the operation. Health-related quality of life improved significantly in both the IUS and hysterectomy groups (change 0.10 [95% CI 0.06-0.14] in both groups) as did other indices of psychological wellbeing. There were no significant differences between the treatment groups except that women with hysterectomy suffered less pain. Overall costs were about three times higher for the hysterectomy group than for the IUS group. INTERPRETATION: The significant improvement in health-related quality of life highlights the importance of treating menorrhagia. During the first year the levonorgestrel-releasing IUS was a cost-effective alternative to hysterectomy in treatment of this disorder.

Correlation between serum inhibin B and other indicators of the ovarian function.

OBJECTIVE: To investigate the correlation between the early follicular phase serum inhibin B levels and other indicators of ovarian reserve. STUDY DESIGN: Seventy-four women aged 24-40 years (mean 32) with different infertility etiologies were investigated in the early follicular phase of a spontaneous mentrual cycle. The volume of the ovaries was measured and the total number of follicles <5 mm in size counted by ultrasound. Serum levels of FSH, estradiol (E2) and inhibin B were measured on the same day. In stepwise regression analysis inhibin B levels were correlated with age, body-mass-index, the ultrasound measurements, cause of infertility, parity, FSH and E2. RESULTS: FSH, BMI and the number of follicles proved to be statistically significant independent predictive factors for the inhibin B levels, FSH and BMI correlating negatively and the number of follicles positively with inhibin B serum concentrations. CONCLUSION: The number of small follicles reflect the inhibin B production of the ovaries. BMI being as strong predictive factor of inhibin B levels as FSH could in part explain the impaired likelihood of conceiving in obese patients.

Visual analogue scale, urinary incontinence severity score and 15 D--psychometric testing of three different health-related quality-of-life instruments for urinary incontinent women.

OBJECTIVE: The purpose of this study is psychometric assessment of disease-specific questionnaire, Urinary Incontinence Severity Score (UISS) and Visual Analogue Scale (VAS) in urinary incontinent women. We also investigated functional relationship between UISS, VAS and 15D-valid, generic health-related quality-of-life (HRQoL) instrument. MATERIALS AND METHODS: Eighty-two incontinent female patients were recruited for the study that included baseline investigation and re-evaluation 13 months (range 6-21 months) after treatment. Twenty-nine control women who had urinary incontinence but were not bothered by it completed the HRQoL measurements. RESULTS: Internal consistency and content validity of UISS was good. Both measures UISS and VAS were reproducible, Spearman's rank correlation between test-retest were 0.88 and 0.85 respectively. The control women's UISS, 15D and VAS scores were significantly lower than the patient's scores (p<0.001, Mann-Whitney U test) which proves to be a good discriminant. The changes in pad test correlated moderately well with those in the VAS and UISS. The UISS, VAS and 15D in the improved group had responsiveness (Guyatt's) statistics: 1.48, 1.74 and -0.80 respectively. CONCLUSION: The UISS and VAS proved to be valid, reproducible and responsive to treatment for UI women. The functionality of the 15D was good but it demonstrated less sensitivity to changes after treatment.

In vitro fertilization in patients with ovarian endometriomas.

OBJECTIVE: The objective of the study was to establish whether operative treatment of recurrent ovarian endometriosis improves the prognosis of in vitro fertilization. METHODS AND MATERIAL: A retrospective analysis of one hundred endometriosis patients admitted to Tampere University Hospital for IVF treatment. Forty-five patients had an ovarian endometrioma during IVF treatment, 36 of the cases being recurrences after a previous operation. Fifty-five patients had ovarian endometriomas operated without recurrence. The patient groups with or without endometriosis did not differ in age, duration of infertility, sperm parameters, amount of gonadotropins required per oocyte and number of retrieved oocytes. RESULTS: The patients with ovarian endometriosis had more embryos (mean 3.9) than women without endometriomas (mean 2.8) (p<0.05) and the respective pregnancy rates per IVF cycle were 38% and 22%. Patients with endometriomas had a live birth rate of 27% compared with 20% in women with no endometriomas. CONCLUSIONS: The presence of a small endometrioma does not reduce the success of IVF treatment.

GnRH analogues and uterine leiomyomas. Effect of hormone replacement therapy on cell proliferation.

Cell proliferation in uterine leiomyomas treated preoperatively with either nafarelin (400 microg/day) for 3 months (7 patients) or nafarelin plus hormone (oestradiol + norethisterone) add-back therapy (6 patients) was investigated by automatic image analysis of frozen tissue sections using immunohistochemistry with anti-proliferating cell nuclear antigen antibody. GnRHa therapy decreased cell proliferation in leiomyomas to a level corresponding to the situation previously seen in postmenopausal leiomyomas. However, there was no consistent correlation between cell proliferation and shrinkage of leiomyomal size. The hormone add-back therapy moderated the influence of GnRHa on cell proliferation and completely blocked a decrease in size of leiomyomas in our patients.

Prognostic factors in controlled ovarian hyperstimulation.

OBJECTIVE: To determine whether the number of retrieved oocytes and the required amount of gonadotropins per oocyte in IVF treatment can be predicted with use of the following independent predictive variables: age, parity, cause of infertility, body mass index, day 3-5 FSH, E2, inhibin B, ovarian volume, the number of follicles, and intraovarian and uterine artery vascular resistance measured by ultrasonography before ovarian hyperstimulation. DESIGN: A retrospective analysis. SETTING: University hospital infertility clinic. PATIENT(S): Seventy-four consecutive women attending the university hospital infertility clinic for IVF treatment. INTERVENTION(S): The investigated factors were measured on day 3-5 of the cycle, in which luteal phase suppression was begun before ovarian hyperstimulation preparatory to IVF. MAIN OUTCOME MEASURE(S): The amount of gonadotropins required per oocyte and the number of retrieved oocytes were correlated with the predictive factors in stepwise regression analysis. RESULT(S): The best predictive factors for the number of oocytes retrieved were FSH, inhibin B, and parity, explaining 25% of the ovarian response. Intraovarian vascular resistance, parity, FSH, and inhibin B best predicted the amount of gonadotropins needed, explaining 44% of the variation. CONCLUSION(S): FSH, inhibin B, and parity were the independent predictive factors for the number of retrieved oocytes. The same factors and intraovarian vascular resistance predicted the required amount of gonadotropins per oocyte. The main part of the ovarian response cannot be predicted using the factors investigated.

Hysterectomy trends in Finland in 1987-1995--a register based analysis.

BACKGROUND: The study objective was to identify trends in the use of hysterectomy by nationwide register based analysis in Finland. METHODS: All women (n=89,069) undergoing hysterectomy in 1987-1995 according to the Finnish Hospital Discharge Register were the numerator. The annual denominator data were obtained from the population database of Statistics Finland. RESULTS: From 1987 to 1992 the hysterectomy rate increased by 22%, from 340 to 414 per 100,000 females, almost half of this being attributable to the changing age structure. From 1993 on, ambiguity in coding laparoscopically assisted vaginal hysterectomies prohibited detailed analyses. However, the overall trend continued at least among women 50 years and over until 1995. The age-adjusted 12% increase from 1987 to 1992 coincided with a rapid increase in operation rates in postmenopausal groups (60% or more among women aged 55 59 and 70-79 years). Among women aged 55-64 years, operations for fibroids and uterine bleeding more than doubled, suggesting an influence of increased use of estrogen replacement therapy. Among all women, operations due to bleeding disorders and genital prolapse showed the largest increase (41% and 42% respectively). Bilateral oophorectomy became more common in all age groups over 46 years. CONCLUSIONS: There was a modest increase in the overall hysterectomy rate. However, the operation became far more common in postmenopausal women, possibly due to the growing use of estrogen replacement therapy. Register data can be used for describing changes in clinical practice, but other methods are needed to confirm the causal relationships underlying the changes.

Activin B: detection by an immunoenzymometric assay in human serum during ovarian stimulation and late pregnancy.

A recently developed immunoenzymometric assay for activin B has been characterized further by measurement during ovarian stimulation and pregnancy. The assay is based on a monoclonal anti-peptide antibody, anti-betaB(101-115). In addition to quantitative analyses, the antibody has been used for immunohistochemical localization of the activin betaB-subunit in human term placenta. Serum samples obtained from patients suffering from tubal factor infertility who were admitted for in-vitro fertilization (IVF) treatment protocols or from patients with proven fertility who were admitted for laparoscopic tubal ligation were collected. The aim was to correlate serum activin B concentrations with other parameters during IVF and with phases of the menstrual cycle. Serum samples obtained from healthy pregnant volunteers were studied to correlate activin B concentrations with clinical parameters. During the IVF treatment protocols, activin B was detectable in all patients studied, and a significant negative correlation was observed between serum activin B and oestradiol concentrations. On the other hand, no significant difference was observed in activin B concentrations when serum samples obtained from patients at different phases of the menstrual cycle were compared, and low concentrations of activin B were observed in the samples obtained from these patients. During pregnancy, a positive correlation was observed between serum activin B concentrations and gestational age. In immunohistochemical analyses of human placental tissue obtained from healthy parturients, the activin betaB-subunit was present in trophoblast, amniotic epithelial and Hofbauer cells. The results suggest a potential clinical application in female reproductive medicine for serum activin B measurements.

Combined laboratory and diary method for objective assessment of menstrual blood loss.

BACKGROUND: To develop an objective measurement system for menstrual blood loss applicable in clinical practice. METHODS: One hundred and fifty-six patients were enrolled in a randomized trial of the treatment of menorrhagia in all five gynecology departments of the university teaching hospitals in Finland. Correlation between venous blood hemoglobin concentration (Hb) and absorbance at 564 nm (A564) was investigated in experiments with blood samples. Amount of collected menstrual blood and menstrual diary data were analyzed. RESULT: Hb concentration and A564 of the blood were linearly correlated (r=0.99). One hundred and fifty-four women (99%) returned used sanitary protection and menstrual diaries. On average, 12% (range 0-57%) of menstrual blood was lost during collection. The median amount of blood recovered from sanitary protection was 89 ml (range 14-724 ml), with 58% (n=90) of the women exceeding 80 ml per cycle. When the spilled blood was taken into account, the corresponding figures were 104 ml (range 15-724 ml) and 66% (n= 101). CONCLUSIONS: The spectrophotometric measurement of venous blood in the conventional alkaline hematin method can be replaced by measurement of Hb concentration. All blood incompletely collected should be recorded. Objective measurement of menstrual blood loss can be applied in routine clinical practice.

Effect of obesity on the response to insulin therapy in noninsulin-dependent diabetes mellitus.

An initial improvement in glycemic control is often followed by gradual deterioration of glycemia during insulin treatment of patients with noninsulin-dependent diabetes mellitus (NIDDM). We examined the causes of such worsening in a 12-month follow-up analysis of 100 insulin-treated NIDDM patients in the Finnish Multicenter Insulin Therapy Study who were treated with either combination therapy with insulin or insulin alone. In the entire study group, glycemic control averaged 9.7 +/- 0.2% at 0 months and 8.0 +/- 0.1%, 8.0 +/- 0.1%, 8.2 +/- 0.1%, and 8.5 +/- 0.2% at 3, 6, 9, and 12 months (P < 0.001 for each time point vs. 0 months). Glycemic control at 12 months was significantly worse than that at 3 (P < 0.001), 6 (P < 0.001), and 9 months (P < 0.02). Baseline body mass index was the most significant predictor of deterioration in glycemic control. During 1 yr, hemoglobin A1c decreased almost 3-fold more (by 1.7 +/- 0.2%; P < 0.001 vs. 0 months) in patients whose baseline weight was below the mean baseline body mass index of 28.1 kg/m2 (nonobese patients) than in those whose weight exceeded 28.1 kg/m2 (obese patients; 0.5 +/- 0.2%; P = NS vs. 0 months; P < 0.01 vs. obese patients). Glycemic control improved similarly over 1 yr in the nonobese subjects and deteriorated similarly in the obese patients regardless of their treatment regimen. Insulin doses, per body weight, were similar in the nonobese and obese patients. The nonobese patients consistently gained less weight during 12 months of combination therapy with insulin (3.5 +/- 0.6 kg at 12 months) than during insulin therapy alone (5.1 +/- 0.6 kg; P < 0.05). The treatment regimen did not influence weight gain in the obese group, who gained 4.4 +/- 1.0 kg during combination therapy with insulin and 4.5 +/- 1.1 kg during insulin therapy alone. We reached the following conclusions: 1) after an initial good response, glycemic control deteriorates more in obese than in nonobese patients with NIDDM; 2) in obese patients, weight gain per se cannot explain the poor glycemic response to combination or insulin therapy, but it may induce a disproportionately large increase in insulin requirements because of greater insulin resistance in the obese than in the nonobese; 3) in nonobese patients, glycemic control improves equally during 1 yr with combination therapy with insulin and insulin alone, but combination therapy with insulin is associated with less weight gain than treatment with insulin alone; 4) weight gain appears harmful, as it is associated with increases in blood pressure and low density lipoprotein cholesterol.