Untreated Diabetes Mellitus Research Articles

A Case of Invasive Paranasal Aspergillosis with Opthalmopathy

Invasive paranasal aspergillosis has been considered to have a poor prognosis. We report a case of orbital apex syndrome due to left ethmoid-sphenoid aspergillosis. A 76-year-old woman with untreated diabetes mellitus, presented with left visual disturbance, oculomotor nerve palsy, ptosis and orbital pain. CT and MRI showed cloudy images with defects of the bone wall in the left posterior ethmoidal sinus. The serological examination revealed aspergillus antigen (+) and high levels of β-D glucan. Therefore, we diagnosed paranasal aspergillosis, and administrated voriconazol preoperatively as an antifungal agent. The patient underwent left ethmoid-sphenoidectomy and biopsy via the endonasal approach. In the histopathologic examination, aspergillus was found around the optic nerve canal. At the present, continucus administration of voriconazol has improved the patient's ptosis and orbital pain, but not her visual disturbance. This case suggests that invasive paranasal aspergillosis has the possibility of visual loss and high mortality rate so that he needs early diagnosis and treatment.

Cervical Spinal Epidural Abscess and Perirenal Abscess Associated with Diabetes Mellitus

A 56-year-old woman was admitted due to fever, thirst, polydipsia, polyuria, posterior cervical pain and lumbago. Hyperglycemia and urine white blood cell elevation were detected. Computed tomography showed left perirenal abscess. Urine culture and blood culture revealed Escherichia coli. We diagnosed perirenal abscess followed by pyelonephritis due to untreated diabetes mellitus. We used 6g of ampicillin-sulbactum daily and from the 10th day 4g of sulfamethoxazole-trimethoprim for perirenal abscess, and 180mg of loxoprofen sodium daily for posterior cervical pain in addition to a diabetic diet and insulin therapy for diabetes mellitus. Although the patient's fever normalized and lumbago improved, posterior cervical pain level increased and bilateral 1, 2 and 3 finger-numbness occurred from the 18th day. Cervical magnetic resonance imaging showed cervical 4, 5 and 6 vertebra inflammation induced spine compression. Removal of the cervical abscess and fixation of the vertebra were performed at the 27th day. Treating diabetes mellitus is important for the prevention of severe infection.

Psoas abscess and bacterial peritonitis caused by urinary tract infection in a patient of liver cirrhosis and diabetes mellitus.

Prognosis of patients with diabetes mellitus or liver cirrhosis can be worsened by the development of a variety of infectious diseases. We describe a case of psoas abscess and bacterial peritonitis in a 58-year-old woman with typeC liver cirrhosis and diabetes mellitus hospitalized after having an elevated temperature caused by urinary tract infection for 2months. The cirrhosis had not been treated and daily self-administration of insulin had been discontinued for the previous 5months. On day2 of hospitalization, vomiting and decreased blood pressure developed. Abdominal computed tomography scan revealed ascites, pneumoperitoneum, and psoas abscess. Laparotomy revealed psoas abscess and bacterial peritonitis without gastrointestinal perforation and psoas abscess perforation. Surgical drainage of the abscess and peritoneal cavity was performed. Immediately after the operation, upper gastrointestinal bleeding, shock, hypoglycemia, and metabolic acidosis developed, followed by hepatic failure, renal insufficiency, and cerebral dysfunction. Death occurred on postoperative day19. Upon autopsy, bacterial peritonitis residue of psoas abscess, and urinary tract infection were confirmed. We surmise that untreated liver cirrhosis and diabetes mellitus is a risk for urinary tract infection that may spread in iliopsoas and free peritoneal space.

Multiple Organ Failure Followed by Intrauterine Klebsiella Pneumoniae Infection Associated with Diabetes Mellitus

A 49-year-old semi-conscious woman was admitted due to fever and dehydration. Disseminated intravascular coagulation (DIC), renal dysfunction and diabetic ketoacidosis were detected. Whole body computed tomography showed multiple nodular lesions in bilateral lungs and kidneys indicating septic emboli, and intrauterine lesions. We diagnosed multiple organ failure followed by intrauterine infection due to untreated diabetes mellitus. Vaginal discharge and blood culture revealed Klebsiella pneumoniae. We used multi-antibiotics for sepsis, respirator at low tidal volume ventilation, 200mg of sivelestat sodium hydrate and 300mg of hydrocortisone for respiratory failure, gabexate mesilate and anti-thrombin III for DIC, transfusion for bleeding from uterus and regular insulin aiming for a blood glucose range of from 80 to 140mg/dl. When we extracted the myoma uteri, the patient's fever subsided and the C-reactive protein became negative. Treating diabetes mellitus is important for the prevention of severe infection.

Effects of early insulin therapy on nuclear factor kappaB pathway in skeletal muscle of diabetes: experiment with rats

To investigate the effect of early insulin therapy on the nuclear factor kappaB (NF-kappaB) pathway and inflammatory cytokine responses in skeletal muscle in type 2 diabetes mellitus (DM). SD rats underwent intraperitoneal injection of streptozotocin to establish DM models and then divided into 5 groups: early un-treated group, early gliclazide treated group (receiving gliclazide since the third day after blood glucose increase for 3 weeks for 3 weeks), early insulin treated group (receiving insulin since the third day after blood glucose increase for 3 weeks for 3 weeks), late un-treated group, and late insulin treated group (receiving insulin since the fourth week after blood glucose increase for 3 weeks). By the end of treatment the rats were killed. Homogenate of skeletal muscle was made. The NF-kappaB P65 DNA binding was assayed by ELISA-based assay kit. Real time PCR was used to detect the mRNA expression levels of the gene of the cytokines: glucose transporter 4 (Glut4), inhibitor kappaB (IkappaBalpha), IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha. And Glut4 and IkappaBalpha protein expression levels were assayed by Western blotting. The Glut4 mRNA level in the skeletal muscle of the untreated DM rats decreased by 59% and the Glut4 protein level in the muscle cell membrane decreased by 69%. Insulin treatment and gliclazide treatment increased the Glut4 mRNA expression by 17% and 13% respectively, increased the Glut4 protein expression in cell membrane by 23% and 10% respectively, and decreased the Glut4 protein expression in the cytoplasm. In the DM rats the IkappaBalpha protein expression in the skeletal muscle was significantly lower (P < 0.05) and the NF-kappaB P65 DNA binding activity increased, and TNF-alpha, IL-1B, and IL-6 expression levels were up-regulated in comparison with the normal control group. Early treatment of insulin and gliclazide increased the IkappaBalpha protein expression, decreased the NF-kappaB P65 DNA binding activity and the TNF-alpha expression in the skeletal muscle. Early insulin treatment inhibits the NFkappaB activity and inflammatory cytokine responses in skeletal muscle that are involved in the amelioration of insulin resistance in type 2 DM. Such results may be due to indirect antiinflammatory effects of insulin relieving glucotoxicity and lipotoxicity in peripheral tissues.

Submandibular Cellulitis Caused by Odontogenic Infection Concomitant with Endogenous Endophthalmitis and Lung Abscess

A 61-year-old man with untreated diabetes mellitus had submandibular cellulitis caused by an odontogenic infection concomitant with endophthalmitis and a lung abscess. Computed tomography showed masses in the right submandibular and lung regions. A biopsy of the anterior chamber aqueous indicated endophthalmitis. The masses in the submandibular and lung regions improved following systemic antibiotic therapy and extraction of the right mandibular molars, the initial symptom in this episode. Although the patient's right eye pain improved, visual acuity did not recover. Cultures from the aqueous and blood were negative. There were no signs of spread of infection to the maxillary sinus, pterygopalatine fossa, and orbit. As there was no inflammatory pathway, it was suggested that haematogenous spread of bacteria had caused inflammatory spread.

Effect of selenium on pancreatic proinflammatory cytokines in streptozotocin-induced diabetic mice

To investigate the effects of selenium on mRNA expressions of proinflammatory cytokines and inducible nitric oxide synthase (iNOS) in the pancreas of streptozotocin-induced diabetic mice, the animals were divided into three groups in this study: a normal control group, an untreated diabetes mellitus group and a selenite-treated diabetes mellitus group. Selenite was administered to the diabetic mice in selenite-treated diabetes mellitus group for 2 weeks with an oral dose of 2 mg/kg body weight per day by gavage. The results showed that pancreatic selenium content and glutathione peroxidase mRNA expression and activity were decreased by 16.0%, 63.9% ( P<.01) and 31.2 % ( P<.01), respectively, in untreated diabetes mellitus group compared with normal control group, and they were significantly increased by 51.0% ( P<.001), 79.7% ( P<.05) and 21.0% ( P<.05), respectively, in selenite-treated diabetes mellitus group compared with untreated diabetes mellitus group. Meanwhile, pancreatic mRNA expressions of proinflammatory cytokines interleukin-1β, tumor necrosis factor-α and interferon-gamma; mRNA expression and activity of iNOS and content of nitric oxide were significantly increased by 133.0% ( P<.01), 164.0% ( P<.001), 111.0% ( P<.01), 101.0% ( P<.001), 73.2% ( P<.001) and 37.6% ( P<.01), respectively, in untreated diabetes mellitus group compared with normal control group, and they were decreased by 43.2% ( P<.01), 37.5% ( P<.01), 33.9 % ( P<.05), 35.5% ( P<.01), 34.9% ( P<.01) and 18.1% ( P<.05), respectively, in selenite-treated diabetes mellitus group compared with untreated diabetes mellitus group. In conclusion, the chosen pharmacological dose of selenium provides partial correction of these effects towards control values. Moreover, the results suggested that the hypoglycemic role of selenium may relate with its inhibiting effect on augmentation of proinflammatory cytokines and reactive oxygen species/reactive nitrogen species by streptozotocin inducing in the pancreas of diabetic mice.

The effect of hyperbaric oxygen therapy on blood vessel function in diabetes mellitus

Prolonged untreated diabetes mellitus leads to microangiopathy, tissue hypoxia and ischemic lesions; it increases the risk for stroke and exacerbates brain tissue damage following ischemia. Patients exhibit advanced atherosclerosis in coronary and cerebral arteries as well as enhanced vascular responsiveness to vasoconstrictors, an attenuated response to vasodilators and impaired autoregulation of cerebral blood flow. Altered endothelial function of arterioles and an impaired vasomotor function of resistance vessels could contribute to altered regulation of regional blood flow and insufficient tissue perfusion in diabetes mellitus. Hyperbaric oxygen therapy is shown to contribute to the healing of ischemic ulcerations in diabetic patients and to improvement of several other pathologic conditions. However, information about the mechanism of how this therapy works is still very limited. We postulate that hyperbaric oxygen therapy has an effect on vascular function by modulating mechanisms of vascular responses to various dilator and constrictor agonists in cerebral resistance vessels, leading to restored vascular reactivity. In accordance to this, the therapy affects production of vasodilators and vasoconstrictors, as well as the vessel-sensitivity to these factors. Furthermore, we hypothesize that hyperbaric oxygen therapy would restore cerebral blood flow regulation that is impaired in diabetics, whereas in contrast to that, chronic intermittent hypoxia would lead to impaired cerebral blood flow. These proposed mechanisms would, if confirmed, represent a valuable advancement in the understanding of this subject.

Enteritis necroticans ‘pigbel’ in a Japanese diabetic adult

Enteritis necroticans 'pigbel' is caused by Clostridium perfringens type C but has rarely been reported in developed countries. A 50-year-old Japanese man with untreated diabetes mellitus (DM) presented with diarrhea and abdominal pain. Intraoperative endoscopic and macroscopic examination disclosed segmental annular mucosal lesions characteristic of clostridial enteritis. Clostridial infection type C was verified on pathological, and immunohistochemical analysis. Although rare, the disease is likely to be underdiagnosed. Hence, the pathology and immunohistochemistry of segmental enteritis with annular mucosal lesions should be examined to establish a diagnosis of enteritis necroticans even in mildly affected patients, and especially those with DM.

In vitro glycation of brain aminophospholipids by acetoacetate and its inhibition by urea

Amino groups of amino acids, nucleic acids and lipids can react non-enzymatically with reducing sugars to form unstable Schiff bases that can then undergo the Amadori rearrangement to form irreversible advanced glycation end products (AGEs). Ketoacidosis is a life-threatening complication in patients with untreated diabetes mellitus and it is characterized by increased circulating ketone body concentrations. Recently, the in vitro glycation of hemoglobin by β-hydroxybutyrate and acetone was described by our laboratory. This study was designed to evaluate the in vitro effect of acetoacetate on brain aminophospholipids at similar concentrations to that observed in ketoacidosis (16.13 mM total ketone bodies). The effect of acetoacetate was compared to that of glucose and the other ketone bodies; β-hydroxybutyrate and acetone. The antiglycating activity of urea and glycylglycine was also investigated. The incubation of aminophospholipids with acetoacetate results in the formation of a new compound with an absorption peak at 280 nm. When this reaction product was analyzed by thin layer chromatography using an elusion system of methanol:chloroform:acetic acid:water (8:1:1:0.4), the R f value obtained (0.24–0.26) was similar to that of the compound formed by aminophospholipids with glucose. In contrast, this reaction product was not detected in those samples containing β-hydroxybutyrate and acetone. The formation of this new compound was inhibited by urea more effectively than glycylglycine. In conclusion, this study provides the evidence that brain aminophospholipids react with acetoacetate forming AGEs and that this glycating effect of acetoacetate was remarkably decreased by urea, suggesting a protective physiological role for urea in the body as it was previously stated. Finally, this information adds knowledge about the contribution of ketoacidosis in the pathophysiology of diabetic complications, especially in type 1 diabetic patients.

Exercise training improves cardiac performance in diabetes: in vivo demonstration with quantitative cine-MRI analyses

Diabetic cardiomyopathy is a distinct myocardial complication of the catabolic state of untreated insulin-dependent diabetes mellitus in the streptozotocin-induced diabetic rat. Exercise training has long been utilized as an effective adjunct to pharmacotherapy in the management of the diabetic heart. However, the in vivo functional benefit(s) of the training programs on cardiac cycle events in diabetes are poorly understood. In this study, we used three groups of Sprague-Dawley rats (sedentary control, sedentary diabetic, and exercised diabetic) to assess the effects of endurance training on the left ventricular (LV) cardiac cycle events in diabetes. At the end of 9 wk of exercise training, noninvasive cardiac functional evaluation was performed by using high-resolution magnetic resonance imaging (9.4 T). An ECG-gated cine imaging protocol was used to capture the LV cardiac cycle events through 10 equally incremented phases. The cardiac cycle phase volumetric profiles showed favorable functional changes in exercised diabetic group, including a prevention of decreased end-diastolic volume and attenuation of increased end-systolic volume that accompanies sedentary diabetes. The defects in LV systolic flow velocity, acceleration, and jerk associated with sedentary diabetes were restored toward control levels in the trained diabetic animals. This magnetic resonance imaging study confirms the prevailing evidence from earlier in vitro and in vivo invasive procedures that exercise training benefits cardiac function in this model of diabetic cardiomyopathy despite the extreme catabolic state of the animals.

Emphysematous pyelonephritis treated with percutaneous catheter drainage and antibiotics

A 58-year-old woman presented acutely with a 3-day history of general weakness, vomiting and fever. For 2 years she had had untreated diabetes mellitus. On examination she was ill, blood pressure was 64/47mmHg, heart rate: 111 beats/min, respiration rate: 28/min and body temperature was 37.28C. The right upper abdomen was tender. There was right loin tenderness. Investigations: white blood cell count 10 380/mm; haemoglobin 7.8 g/dl; haematocrit 23.1%; platelet count 36 000/mm; blood urea nitrogen 70mg/dl; serum creatinine 6.2mg/dl; glucose 302mg/dl; C-reactive protein 21.4mg/dl; sodium 129mEq/l; potassium 4.1mEq/l; chloride 98mEq/l; and total CO2 8.9mEq/l. An arterial blood gas pH 7.242, pO2 60mmHg, pCO2 22mmHg and bicarbonate 9.3mEq/l. A plain abdominal film showed air density in the right pelvocalyceal system and upper ureter (Figure 1). Computed tomography (CT) of the abdomen without contrast confirmed the presence of air in the pelvicalyceal system and upper ureter of the enlarged right kidney (Figure 2). Six hours after admission, she became hypotensive and unconscious. She was intubated and ventilated. She received fluid resuscitation, emergency haemodialysis, and intravenous piperacillin and tazobactam. A percutaneous catheter was inserted into the pelvicalyceal system of the right kidney and drained turbid fluid. Blood and urine cultures grew Escherichia coli. The catheter was removed on day 12 because of disappearance of air in right excretory system at follow-up CT. Antibiotic therapy was continued for 4 weeks. She survived but did not recover renal function.

Frequency of undiagnosed and untreated diabetes mellitus in patients with acute coronary syndromes

The current epidemic of obesity warrants aggressive screening for associated comorbid conditions; namely, the metabolic syndrome and diabetes mellitus. Approximately 25–30% of patients with acute coronary syndrome have diabetes. Of the remaining patients, most have a spectrum of abnormal glucose metabolism, including previously undiagnosed impaired fasting glucose and diabetes mellitus. This article reviews the current literature and the author’s own experience of this subject, as well as highlighting effective new agents in treating diabetes.

Effects of benazepril on renal function and kidney expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in diabetic rats

Excessive deposition of extracellular matrix (ECM) in the kidney is the hallmark of diabetic nephropathy. Increased matrix synthesis has been well documented but the effects of diabetes on degradative pathways, particularly in the in vivo setting. The renal protective effect of these pathways on matrix accumulation has not been fully elucidated. The present study was undertaken to investigate the activity of matrix metalloproteinase-2 (MMP-2), the expression of MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) in kidney tissues of diabetic rats, and to explore the degradative pathway of type IV collagen (IV-C) and the renal protective effects of ACE inhibition-benazepril. Twenty-four healthy male Wistar rats were divided randomly into normal control group (NC group), untreated diabetes mellitus group (DM group), and diabetes mellitus group treated with benazepril (DL group). The rat model of diabetes mellitus was induced by intraperitoneal injection of streptozocin (60 mg/kg). After the establishment of DM model, benazepril (10 mg.kg(-1).d(-1)) was given to the DL group for 12 weeks, and the same volume of water was given to the other two groups. At the end of 12 weeks, renal function was evaluated with 24-hour urinary protein (Upro), clearance of creatinine (Ccr), and blood urea nitrogen (BUN). MMP-2 activity was determined by gelatin zymography. The levels of MMP-2, TIMP-2 and collagen IV (IV-C) protein in the kidney tissue were assessed by immunohistochemistry. The gene expression of MMP-2 and TIMP-2 was measured by reverse transcription polymerase chain reaction (RT-PCR). The levels of BUN, Upro and Ccr in the DM group were higher than those in the NC group. In the DM group, the mRNA, enzymatic activity and proteins of MMP-2 decreased, but the expressions of IV-C and TIMP-2 increased. All diabetes-associated changes in renal function and MMP/TIMP were attenuated after benazepril treatment with reduced IV-C accumulation. The changes of MMP-2 and TIMP-2 expressions in kidney tissues of diabetes rats may contribute to the occurrence and progression of diabetic nephropathy. Benazepril could exert protective effects on diabetic nephropathy, owing to the upregulation of MMP-2 and downregulation of TIMP-2 expressions, which further inhibits the excessive deposition of extracellular matrix in the glomerulus.

Measurements of growth hormone and insulin-like growth factor 1 in cats with diabetes mellitus

Serum concentrations of insulin-like growth factor 1 (IGF-1) and growth hormone were measured in 25 cats with untreated diabetes mellitus (11 of which were used for follow-up measurements, one to...

Rheumatological manifestations of diabetes mellitus - a review

The aim of this paper is to review literature on rheumatological manifestations of diabetes mellitus. An English language literature search using Medline and PubMed (1968 January to December 2003) was done to assess research / review articles on rheumatological manifestations of diabetes mellitus A variety of rheumatological conditions are strongly associated with diabetes mellitus including limited joint mobility, specific arthropathies of the hand (carpal tunnel syndrome, Dupytrens contracture, flexor tenosynovitis and diabetic sclerodactyly), shoulder (adhesive capsulitis-frozen shoulder, and calcific periarthritis) and spontaneous infarction of skeletal muscle. On the other hand, there are some conditions that are weakly associated with diabetes mellitus including osteoarthritis and chondrocalcinosis. The likely pathogenetic mechanisms, diagnosis and the management of these conditions are discussed. Poorly controlled and untreated diabetes mellitus of a long duration may be associated with some rheumatological conditions. The presence of these rheumatological conditions should prompt clinicians in screening the individual for diabetes mellitus.Keywords: diabetes mellitus, musclo-skeletal Nigerian Medical Practitioner Vol. 48(3) 2005: 77-83

Insulin action in the brain contributes to glucose lowering during insulin treatment of diabetes

To investigate the role of brain insulin action in the pathogenesis and treatment of diabetes, we asked whether neuronal insulin signaling is required for glucose-lowering during insulin treatment of diabetes. Hypothalamic signaling via the insulin receptor substrate-phosphatidylinositol 3-kinase (IRS-PI3K) pathway, a key intracellular mediator of insulin action, was reduced in rats with uncontrolled diabetes induced by streptozotocin (STZ-DM). Further, infusion of a PI3K inhibitor into the third cerebral ventricle of STZ-DM rats prior to peripheral insulin injection attenuated insulin-induced glucose lowering by approximately 35%-40% in both acute and chronic insulin treatment paradigms. Conversely, increased PI3K signaling induced by hypothalamic overexpression of either IRS-2 or protein kinase B (PKB, a key downstream mediator of PI3K action) enhanced the glycemic response to insulin by approximately 2-fold in STZ-DM rats. We conclude that hypothalamic insulin signaling via the IRS-PI3K pathway is a key determinant of the response to insulin in the management of uncontrolled diabetes.

Effects of Treatment for Diabetes Mellitus on Circulating Vascular Progenitor Cells

The circulating endothelial progenitor cells (EPCs) have an important role in angiogenesis, and the smooth muscle progenitor cells (SMPCs) participate in atherosclerosis. However, little is known about the effects of treatment of diabetes mellitus (DM) on EPCs and SMPCs. Therefore, we investigated the relations between the number of circulating vasucular progenitor cells before and after the treatment for DM. Ten previously untreated DM patients were enrolled in this study. Blood samples were collected before and after treatment. The peripheral mononuclear cells were purified and cultured to differentiate them into EPCs and SMPCs. After two weeks, the number of EPCs was determined by Dil-labeled acetylated low density lipoprotein and lectin binding. The number of SMPCs was evaluated by immunocytochemical staining of α-smooth muscle actin. Before treatment, the number of EPCs and SMPCs was significantly related to hemoglobin A1c and blood sugar. Serial examination revealed that improvement of glycemic control significantly increased the number of both EPCs and SMPCs. DM reduces the number of circulating EPCs and SMPCs according to its severity, and treatment of DM significantly increases the number of EPCs and SMPCs, which may be involved in angiogenesis and atherosclerosis in diabetes.

Hypothalamic paraventricular nucleus, but not vasopressin, participates in chronic hyperactivity of the HPA axis in diabetic rats

Diabetes mellitus (DM), as chronic stress activates the hypothalamo-pituitary-adrenocortical axis. We examined whether arginine vasopressin (AVP) and the hypothalamic paraventricular nucleus (PVN) participate in DM-induced chronic stress symptoms. AVP-deficient Brattleboro or PVN-lesioned Wistar rats were used with heterozygous or sham-operated controls. The rats were studied 2 wk after a single injection of streptozotocin. The appearance of DM (enhanced water consumption and blood glucose elevation) and the chronic stress-like somatic changes (body weight decrease, thymus involution, adrenal gland hypertrophy) were not influenced by the lack of AVP. By contrast, PVN lesion significantly attenuated DM-induced thymus involution and adrenal gland hypertrophy as well as the increase in water consumption. The corticotropin-releasing hormone mRNA in PVN was diminished by DM and elevated by the lack of AVP without interaction. DM elevated the proopiomelanocortin (POMC) mRNA in the anterior lobe of the pituitary. The lack of AVP had no effect, whereas lesioning the PVN significantly diminished the elevation. The elevated basal corticosterone plasma levels detectable in DM were influenced neither by the lack of AVP nor by lesioning the PVN. Thus the lack of AVP had no influence on DM-induced chronic stress symptoms, but lesioning the PVN attenuated part of them. However, the lack of elevation in POMC mRNA after PVN lesion, together with the maintained corticosterone elevation, suggests that direct adrenal gland activation occurs in untreated DM.

Gestational diabetes: The consequences of not treating

Untreated gestational diabetes mellitus carries significant risks of perinatal morbidity at all severity levels; treatment will enhance outcome. A matched control of 555 gravidas, gestational diabetes mellitus diagnosed after 37 weeks, were compared with 1110 subjects treated for gestational diabetes mellitus and 1110 nondiabetic subjects matched from the same delivery year for obesity, parity, ethnicity, and gestational age at delivery. The nondiabetic subjects and those not treated for gestational diabetes mellitus were matched for prenatal visits. A composite adverse outcome was 59% for untreated, 18% for treated, and 11% for nondiabetic subjects. A 2- to 4-fold increase in metabolic complications and macrosomia/large for gestational age was found in the untreated group with no difference between nondiabetic and treated subjects. Comparison of maternal size, parity, and disease severity revealed a 2- to 3-fold higher morbidity rate for the untreated groups, compared with the other groups. Untreated gestational diabetes mellitus carries significant risks for perinatal morbidity in all disease severity levels. Timely and effective treatment may substantially improve outcome.