Gunjan Y Gandhi

Mayo Foundation for Medical Education and Research, Rochester, Michigan, United States

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Publications (22)213.66 Total impact

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    ABSTRACT: Hyperprolactinemia is a common endocrine disorder that can be associated with significant morbidity. We conducted a systematic review and meta-analyses of outcomes of hyperprolactinemic patients, including microadenomas and macroadenomas, to provide evidence-based recommendations for practitioners. Through this review, we aimed to compare efficacy and adverse effects of medications, surgery and radiotherapy in the treatment of hyperprolactinemia. We searched electronic databases, reviewed bibliographies of included articles, and contacted experts in the field. Eligible studies provided longitudinal follow-up of patients with hyperprolactinemia and evaluated outcomes of interest. We collected descriptive, quality and outcome data (tumor growth, visual field defects, infertility, sexual dysfunction, amenorrhea/oligomenorrhea and prolactin levels). After review, 8 randomized and 178 nonrandomized studies (over 3,000 patients) met inclusion criteria. Compared to no treatment, dopamine agonists significantly reduced prolactin level (weighted mean difference, -45; 95% confidence interval, -77 to -11) and the likelihood of persistent hyperprolactinemia (relative risk, 0.90; 95% confidence interval, 0.81 to 0.99). Cabergoline was more effective than bromocriptine in reducing persistent hyperprolactinemia, amenorrhea/oligomenorrhea, and galactorrhea. A large body of noncomparative literature showed dopamine agonists improved other patient-important outcomes. Low-to-moderate quality evidence supports improved outcomes with surgery and radiotherapy compared to no treatment in patients who were resistant to or intolerant of dopamine agonists. Our results provide evidence to support the use of dopamine agonists in reducing prolactin levels and persistent hyperprolactinemia, with cabergoline proving more efficacious than bromocriptine. Radiotherapy and surgery are useful in patients with resistance or intolerance to dopamine agonists.
    Systematic reviews. 07/2012; 1(1):33.
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    ABSTRACT: We report the case of a 66-year-old woman with tumor-induced osteomalacia (TIO) caused by fibroblast growth factor 23 (FGF-23) secreting mesenchymal tumor localized in a lumbar vertebra and review other cases localized to the axial skeleton. She presented with nontraumatic low back pain and spontaneous bilateral femur fractures. Laboratory testing was remarkable for low serum phosphorus, phosphaturia, and significantly elevated serum FGF-23 level. Magnetic resonance imaging (MRI) of the lumbar spine showed a focal lesion in the L-4 vertebra which was hypermetabolic on positron emission tomography (PET) scan. A computed tomography (CT) guided needle biopsy showed a low grade spindle cell neoplasm with positive FGF-23 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR), confirming the diagnosis of a phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT). The patient elected to have surgery involving anterior resection of L-4 vertebra with subsequent normalization of serum phosphorus. Including the present case, we identified 12 cases of neoplasms localized to spine causing TIO. To our knowledge, this paper represents the first documented case of lumbar vertebra PMT causing TIO. TIO is a rare metabolic bone disorder that carries a favorable prognosis. When a lesion is identifiable, surgical intervention is typically curative.
    Case reports in endocrinology. 01/2012; 2012:185454.
  • Dara L Eckerle Mize, Gunjan Y Gandhi
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    ABSTRACT: QUESTION Which interventions prevent foot ulcers in at-risk patients with diabetes? REVIEW SCOPE Included studies evaluated interventions for primary or secondary prevention of foot ulcers in at-risk patients with diabetes. REVIEW METHODS MEDLINE (1960 to Apr 2010), Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, International Clinical Trials Registry Platform, Google databases, and reference lists of included studies and reviews were searched for published and unpublished randomized controlled trials (RCTs). 11 published studies and 1 unpublished study met the selection criteria. Studies included patients with past foot ulcers or those at high risk for foot ulcers (e.g., neuropathy plus foot deformity or amputation). Randomization was inadequate in 2 studies; the results of these studies are not reported below. Of the remaining 10 studies, 3 had adequate allocation concealment, 6 had an acceptable dropout rate, 3 used intention-to-treat analysis, 5 had blinding of providers, and none had blinding of patients. MAIN RESULTS Results of interventions to prevent foot ulcers were inconsistent (Table). CONCLUSION Evidence for the effectiveness of interventions to prevent foot ulcers in at-risk patients with diabetes is limited. INTERVENTIONS TO PREVENT FOOT ULCERS IN AT-RISK PATIENTS WITH DIABETES* Intervention typeInterventions vs controls (n)†Main findingsPatient education and/or caretaker monitoring1 hour of education vs NR (203)Limb amputation, recurrent ulcer, or foot infection: 10% vs 28% of limbs (P = NR)Multifaceted intervention including foot-care education, behavior contract, and regular reminders vs UC (NR)Intervention reduced serious foot lesions (P = 0.05)Individual education vs UC (172)Foot ulcers: NS at 6 mo and 12 moIndex group (included diabetic foot clinic for 127 high-risk patients) vs control (2001)Intervention reduced major amputations (P = NR); groups did not differ for minor amputations or ulcerationsTherapeutic footwear or insolesInsole 1 vs insole 2 vs usual footwear (400)Foot ulcers: NS between the 3 groupsShear-reducing insole vs UC (299)Foot ulcer recurrence in 78 patients with a previous ulcer: 2.5% vs 34%, RRR 90% Foot ulcers in patients without previous plantar foot ulcers: NSBone debridementSurgical bone debridement vs NR (43)Foot ulcers: 3 vs 8 (P < 0.01)Plantar foot TGATTGAT + UC vs UC (85)Ulcers or Charcot fractures at 6 mo: 2% vs 20% (P = 0.01)TGAT + UC vs structured foot exam vs UC (173)Foot ulcers at 15 mo: 8.5% vs 30% in foot exam and usual care groups (P = NR)TGAT + UC vs UC (225)Foot ulcers: 4.7% vs 12%, RRR 62%*NR = not reported; NS = not significant; TGAT = temperature-guided avoidance therapy; UC = usual care; other abbreviations defined in Glossary.†1 trial reported for each comparison.
    Annals of internal medicine 10/2011; 155(8):JC4-8. · 13.98 Impact Factor
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    ABSTRACT: We conducted a systematic review and meta-analysis to assess the efficacy of continuous glucose monitoring (CGM) in improving glycemic control and reducing hypoglycemia compared to self-monitored blood glucose (SMBG). We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and Scopus for randomized trials of adults and children with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Pairs of reviewers independently selected studies, assessed methodological quality, and extracted data. Meta-analytic estimates of treatment effects were generated using a random-effects model. Nineteen trials were eligible and provided data for meta-analysis. Overall, CGM was associated with a significant reduction in mean hemoglobin A1c [HbA1c; weighted mean difference (WMD) of -0.27% (95% confidence interval [CI] -0.44 to -0.10)]. This was true for adults with T1DM as well as T2DM [WMD -0.50% (95% CI -0.69 to -0.30) and -0.70 (95% CI, -1.14 to -0.27), respectively]. No significant effect was noted in children and adolescents. There was no significant difference in HbA1c reduction between studies of real-time versus non-realtime devices (WMD -0.22%, 95% CI, -0.59 to 0.15 versus -0.30%, 95% CI, -0.49 to -0.10; p for interaction 0.71). The quality of evidence was moderate due to imprecision, suggesting increased risk for bias. Data for the incidence of severe or nocturnal hypoglycemia were sparse and imprecise. In studies that reported patient satisfaction, users felt confident about the device and gave positive reviews. Continuous glucose monitoring seems to help improve glycemic control in adults with T1DM and T2DM. The effect on hypoglycemia incidence is imprecise and unclear. Larger trials with longer follow-up are needed to assess the efficacy of CGM in reducing patient-important complications without significantly increasing the burden of care for patients with diabetes.
    Journal of diabetes science and technology 07/2011; 5(4):952-65.
  • K L Venkatachalam, Gunjan Y Gandhi
    Evidence-based medicine 12/2009; 14(6):177.
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    Michelle A Kovalaske, Gunjan Y Gandhi
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    ABSTRACT: Hyperglycemia in the critically ill is a well-known phenomenon, even in those without known diabetes. The stress response is due to a complex interplay between counter-regulatory hormones, cytokines, and changes in insulin sensitivity. Illness/infection, overfeeding, medications (e.g., corticosteroids), insufficient insulin, and/or volume depletion can be additional contributors. Acute hyperglycemia can adversely affect fluid balance (through glycosuria and dehydration), immune and endothelial function, inflammation, and outcome. While there are several insulin infusion protocols that are able to safely and effectively treat hyperglycemia, the bulk of accumulated evidence does not support a causal relationship between acute hyperglycemia and adverse outcomes in the medical intensive care unit. Meta-analysis of randomized controlled trials suggests there is no benefit to tightening glucose control to normal levels compared to a reasonable and achievable goal of 140 to 180 mg/dl. There is a significantly increased risk of hypoglycemia. Although there is some evidence that patients without known diabetes have worse outcomes than those with known diabetes, more recent evidence is conflicting. Glycemic control in critically ill patients should not be neglected, as studies have not tested tight versus no/poor control, but tight versus good control. A moderate approach to managing critical illness hyperglycemia seems most prudent at this juncture. Future research should ascertain whether there are certain subgroups of patients that would benefit from tighter glycemic goals. It also remains to be seen if tight glucose control is beneficial once hypoglycemia is minimized with technological advances such as continuous glucose monitoring systems.
    Journal of diabetes science and technology 11/2009; 3(6):1330-41.
  • Michelle A Kovalaske, Gunjan Y Gandhi
    Annals of internal medicine 09/2009; 151(4):JC2-5. · 13.98 Impact Factor
  • Michelle A Kovalaske, Gunjan Y Gandhi
    Annals of internal medicine 09/2009; 151(4):JC2-4, JC2-5. · 13.98 Impact Factor
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    Michelle A Kovalaske, Gunjan Y Gandhi
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    ABSTRACT: Incretins such as glucagon-like peptide-1 (GLP-1) are gut-derived hormones that stimulate insulin secretion and suppress glucagon secretion, thus playing a key role in glucose homeostasis. While incretin mimetics and enhancers are approved for treatment of outpatients with diabetes, evidence is only starting to accumulate regarding the therapeutic potential of incretins in hospitalized patients. Small exploratory studies suggest that GLP-1 safely reduces hyperglycemia without causing hypoglycemia, a key advantage over insulin if efficacy is established in larger studies. Potential limitations include the need for a continuous infusion for delivery, attenuation but not normalization of glucose levels, increased deceleration of gastric emptying and nausea. The exact mechanism of action, dosing, adverse effects, patient subgroups that would be most suitable and safety of combination treatment with insulin remain to be studied. While promising, additional research is required studying effects on hard clinical endpoints.
    Critical care (London, England) 08/2009; 13(4):161. · 4.72 Impact Factor
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    ABSTRACT: Concerns about the safety and efficacy of diabetes interventions persist, in part because randomized clinical trials (RCTs) have not measured their effect on patient-important outcomes, ie, death and quality of life (morbidity, pain, function). To systematically determine the extent to which ongoing and future RCTs in diabetes will ascertain patient-important outcomes. On November 10, 2007, we searched primary RCT registries ClinicalTrials.gov (http://www.clinicaltrials.gov), International Standard Randomized Controlled Trial Number Register (http://isrctn.org), and Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au). We identified phase 2 through 4 RCTs enrolling patients with diabetes. Of 2019 RCTs, 1054 proved eligible. We randomly sampled 50% of the eligible RCTs (527 of 1054) and selected 436 registered since registration became mandatory (2004). Pairs of reviewers working independently collected study characteristics and determined the outcomes measured and their type (physiological outcomes, surrogate outcomes thought to reflect an increased risk for patient-important outcomes, and patient-important outcomes). Of the 436 registered RCTs included in this analysis, 24 (6%) had not started enrollment, 109 (25%) were actively enrolling, and 303 (69%) had completed enrollment. Primary outcomes were patient-important outcomes in only 78 of 436 RCTs (18%; 95% confidence interval [CI], 14%-22%), physiological and laboratory outcomes in 69 of 436 (16%; 95% CI, 13%-20%), and surrogate outcomes in 268 of 436 (61%; 95% CI, 57%-66%). Patient-important outcomes were reported as primary or secondary outcomes in 201 of 436 (46%; 95% CI, 41%-51%). In multivariate analysis, large trials (odds ratio [OR], 1.10; 95% CI, 1.02-1.19 for every additional 100 patients) and trials of longer duration (OR, 1.03; 95% CI, 1.01-1.06 for every additional 30 days) were more likely while parallel design RCTs (OR, 0.15; 95% CI, 0.05-0.44) and type 2 diabetes trials (OR, 0.23; 95% CI, 0.09-0.61) were less likely to assess patient-important outcomes as a primary outcome. In this sample of registered ongoing RCTs in diabetes, only 18% included patient-important outcomes as primary outcomes.
    JAMA The Journal of the American Medical Association 06/2008; 299(21):2543-9. · 29.98 Impact Factor
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    ABSTRACT: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of perioperative insulin infusion on outcomes important to patients. We used 6 search strategies including an electronic database search of MEDLINE, EMBASE, and Cochrane CENTRAL, from their inception up to May 1, 2006, and included RCTs of perioperative insulin infusion (with or without glucose targets) measuring outcomes in patients undergoing any surgery. Pairs of reviewers working independently assessed the methodological quality and characteristics of included trials and abstracted data on perioperative outcomes (ie, outcomes that occurred during hospitalization or within 30 days of surgery). We identified 34 eligible trials. In the 14 trials that assessed mortality, there were 68 deaths among 2192 patients randomized to insulin infusion compared with 98 deaths among 2163 patients randomized to control therapy (random-effects pooled relative risk, 0.69; 95% confidence interval [CI], 0.51-0.94; 99% CI, 0.46-1.04; I2, 0%; 95% CI, 0.0%-47.4%). Hypoglycemia increased in the intensively treated group (20 trials, 119/1470 patients in insulin infusion vs 48/1476 patients in control group; relative risk, 2.07; 95% CI, 1.29-3.32; 99% CI, 1.09-3.88; I2, 31.5%; 95% CI, 0.0%-59.0%). No significant effect was seen in any other outcomes. The available mortality data represent only 40% of the optimal information size required to reliably detect a plausible treatment effect; potential methodological and reporting biases weaken inferences. Perioperative insulin infusion may reduce mortality but increases hypoglycemia in patients who are undergoing surgery; however, mortality results require confirmation in large and rigorous RCTs.
    Mayo Clinic Proceedings 05/2008; 83(4):418-30. · 5.79 Impact Factor
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    ABSTRACT: Although recent trial results of anti-CD3 therapy are promising, there have been conflicting results of various immunotherapeutic agents used in patients with type 1 diabetes. We conducted a systematic review and meta-analysis to determine the efficacy of nonantigen-based immunotherapeutic approaches for preservation of beta-cell function in patients with type 1 diabetes. We searched MEDLINE, EMBASE, Cochrane CENTRAL, reference lists, and content expert files up to September 2006. Eligible studies were randomized controlled trials (RCTs) of antiproliferative agents (methotrexate, azathioprine), monoclonal antibodies (CD3, CD4), T-cell inhibitors (cyclosporin) and other immunotherapeutic agents (photopheresis, linomide, fusidin, buffy coat, intravenous immunoglobulin, BCG, nicotinamide) in patients with newly diagnosed type 1 diabetes followed for > or = 6 months. Pairs of reviewers working independently and with adequate reliability assessed the trials' methodological quality, collected data, and conducted random-effects meta-analyses on measures of preservation of beta-cell function (e.g. C-peptide secretion, insulin independence). Of the 299 potentially relevant articles identified after an initial search, 20 trials met selection criteria. Meta-analysis of 20 trials (n = 1187 patients) found a small to moderate improvement in beta-cell function with immunotherapy [vs. placebo, effect size 0.37, 95% confidence interval (CI) 0.14-0.6] but there was moderate inconsistency in results across trials (I(2) 65%, 95% CI 39-77%). Subgroup analysis suggested a greater effect of cyclosporin and antiproliferative agents on beta-cell function when used for > or = 6 months (pooled effect size 0.77 vs. -0.11, respectively; P(interaction) = 0.002). Long-term immunotherapy may preserve beta-cell function in newly diagnosed patients with type 1 diabetes. Patients and clinicians must await the conduct of rigorous trials reporting on diabetes resolution, adverse events, and other patient-important outcomes.
    Clinical Endocrinology 01/2008; 69(2):244-52. · 3.40 Impact Factor
  • Victor M Montori, Gunjan Y Gandhi, Gordon H Guyatt
    The Lancet 10/2007; 370(9593):1104-6. · 39.21 Impact Factor
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    ABSTRACT: To determine the prevalence and characteristics of endocrinopathies at diagnosis of POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome. From January 1, 1960, through June 30, 2006, we identified 170 patients with POEMS syndrome in the Mayo Clinic dysproteinemia database. We abstracted information about endocrine abnormalities from their medical records. Of the 170 patients with POEMS syndrome during the entire study period, the 64 patients seen after 2000 had more complete endocrine evaluations; of these 64 patients, 54 (84%) had a recognized endocrinopathy (38 men; median age, 50 years; interquartile range, 43-59 years). Hypogonadism was the most common endocrine abnormality; 26 (79%) of 33 men had subnormal total testosterone levels, and 10 men had gynecomastia. Among the 35 patients with measured prolactin levels, 7 men and 3 women had elevated levels. Hypothyroidism was noted in 17 men and 11 women. Abnormalities in glucose metabolism were present in 24 (48%) of 50 patients; 16 patients had impaired fasting glucose levels, and 8 were diagnosed as having diabetes. Adrenal insufficiency (defined by an abnormal response of cortisol to stimulation with standard high-dose [250 microg] synthetic adrenocorticotropic hormone) was noted in 6 of 9 patients tested. Fourteen (27%) of 51 patients tested had hypocalcemia. Twenty-nine (54%) of 54 patients had evidence of multiple endocrinopathies in the 4 major endocrine axes (gonadal, thyroid, glucose, and adrenal). The high prevalence of endocrinopathy in our study, to our knowledge the largest published series of POEMS cases, calls for a thorough endocrine investigation in patients presenting with this syndrome.
    Mayo Clinic Proceedings 08/2007; 82(7):836-42. · 5.79 Impact Factor
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    ABSTRACT: Intravenous insulin protocols are increasingly common in the intensive care unit to maintain normoglycemia. Little is known about the accuracy of point-of-care glucometers for measuring glucose in this patient population or the impact of sample source (capillary, arterial, or venous whole blood) on the accuracy of glucometer results. We compared capillary, arterial, and venous whole blood glucose values with laboratory plasma glucose values in 20 patients after cardiac surgery. All 4 samples (capillary, arterial, and venous whole blood and laboratory plasma glucose) were analyzed hourly for the first 5 hours during intravenous insulin therapy in the intensive care unit. There were no significant differences between median capillary whole blood (149 mg/dL [8.3 mmol/L]) and laboratory plasma (151 mg/dL [8.4 mmol/L]) glucose levels. The median arterial (161 mg/dL [8.9 mmol/L]) and venous (162 mg/dL [9.0 mmol/L]) whole blood glucose levels were significantly higher than the median laboratory plasma glucose level. Capillary whole blood glucose levels correlate most closely with laboratory plasma glucose levels in patients receiving intensive intravenous insulin therapy after cardiac surgery.
    American Journal of Clinical Pathology 07/2007; 127(6):919-26. · 2.88 Impact Factor
  • Gunjan Y Gandhi, Victor M Montori
    New England Journal of Medicine 03/2007; 356(13):1379-80; author reply 1380. · 54.42 Impact Factor
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    ABSTRACT: It is not known whether rigorous intraoperative glycemic control reduces death and morbidity in cardiac surgery patients. To compare outcomes of intensive insulin therapy during cardiac surgery with those of conventional intraoperative glucose management. A randomized, open-label, controlled trial with blinded end point assessment. Tertiary care center. Adults with and without diabetes who were undergoing on-pump cardiac surgery. The primary outcome was a composite of death, sternal infections, prolonged ventilation, cardiac arrhythmias, stroke, and renal failure within 30 days after surgery. Secondary outcome measures were length of stay in the intensive care unit and hospital. Patients were randomly assigned to receive continuous insulin infusion to maintain intraoperative glucose levels between 4.4 (80 mg/dL) and 5.6 mmol/L (100 mg/dL) (n = 199) or conventional treatment (n = 201). Patients in the conventional treatment group were not given insulin during surgery unless glucose levels were greater than 11.1 mmol/L (>200 mg/dL). Both groups were treated with insulin infusion to maintain normoglycemia after surgery. Mean glucose concentrations were statistically significantly lower in the intensive treatment group at the end of surgery (6.3 mmol/L [SD, 1.6] [114 mg/dL {SD, 29}] in the intensive treatment group vs. 8.7 mmol/L [SD, 2.3] [157 mg/dL {SD, 42}] in the conventional treatment group; difference, -2.4 mmol/L [95% CI, -2.8 to -1.9 mmol/L] [-43 mg/dL {CI, -50 to -35 mg/dL}]). Eighty two of 185 patients (44%) in the intensive treatment group and 86 of 186 patients (46%) in the conventional treatment group had an event (risk ratio, 1.0 [CI, 0.8 to 1.2]). More deaths (4 deaths vs. 0 deaths; P = 0.061) and strokes (8 strokes vs. 1 strokes; P = 0.020) occurred in the intensive treatment group. Length of stay in the intensive care unit (mean, 2 days [SD, 2] vs. 2 days [SD, 3]; difference, 0 days [CI, -1 to 1 days]) and in the hospital (mean, 8 days [SD, 4] vs. 8 days [SD, 5]; difference, 0 days [CI, -1 to 0 days]) was similar for both groups. This single-center study used a composite end point and could not examine whether outcomes differed by diabetes status. Intensive insulin therapy during cardiac surgery does not reduce perioperative death or morbidity. The increased incidence of death and stroke in the intensive treatment group raises concern about routine implementation of this intervention.
    Annals of internal medicine 02/2007; 146(4):233-43. · 13.98 Impact Factor
  • Gunjan Y Gandhi, William L Isley
    ACP journal club 01/2007; 146(1):11.
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    Gunjan Y Gandhi, Brian A Swiglo
    ACP journal club 01/2007; 146(1):8.
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    ABSTRACT: To determine the temporal trends in prevalence of confirmed diabetes mellitus (DM), time from the date DM criteria were met to myocardial infarction (MI), and impact of DM on survival. A retrospective cohort design was used to identify residents of Olmsted County, Minnesota, with incident MI from 1979 to 1998. The MI cases were characterized according to prevalent DM. Cases with and without DM were followed up for vital status until January 1, 2003. Of 2171 MI cases, 364 (17%) met criteria for prevalent DM. In the age- and sex-adjusted logistic regression models, the odds of prevalent DM Increased 3% with each Increasing year between 1979 and 1998 (95% confidence Interval [CI], 1%-5%; P=.007). Survival for MI cases with DM was unchanged between 1979-1983 and 1994-1998 (P=.74). For all MI cases, age-, sex-, and DM-adjusted risk of death decreased 3% from 1979 to 1998 (95% CI, 1%-5%) per year for 28-day survival (P=.02) and 2% (95% CI, 1%-3%) per year for 5-year survival (P=.02). There was a significant adverse effect of DM on 5-year survival after MI (age-, sex-, and calendar year-adjusted hazard ratio, 1.70; 95% CI, 1.38-2.09; P<.001). The adverse effect of DM persisted after adjusting for other cardiovascular disease risk factors, MI severity, and reperfusion therapy (hazard ratio, 1.66; 95% CI, 1.34-2.05; P<.001) and was unchanged over time (interaction between DM and calendar year, P=-.63). These data indicate that the prevalence of DM among patients with MI is increasing and that its adverse impact on survival after MI remains unchanged.
    Mayo Clinic Proceedings 08/2006; 81(8):1034-40. · 5.79 Impact Factor