Central Regulation of Glucose Production May Be Impaired in Type 2 Diabetes.

The challenges of achieving optimal glycemic control in type 2 diabetes highlight the need for new therapies. Inappropriately elevated endogenous glucose production (EGP) is the main source of hyperglycemia in type 2 diabetes. Because activation of central ATP-sensitive potassium (KATP) channels suppresses EGP in nondiabetic rodents and humans, this study examined whether type 2 diabetic humans and rodents retain central regulation of EGP. The KATP channel activator diazoxide was administered in a randomized, placebo-controlled crossover design to eight type 2 diabetic subjects and seven age- and BMI-matched healthy control subjects. Comprehensive measures of glucose turnover and insulin sensitivity were performed during euglycemic pancreatic clamp studies following diazoxide and placebo administration. Complementary rodent clamp studies were performed in Zucker Diabetic Fatty rats. In type 2 diabetic subjects, extrapancreatic KATP channel activation with diazoxide under fixed hormonal conditions failed to suppress EGP, whereas matched control subjects demonstrated a 27% reduction in EGP (P = 0.002) with diazoxide. Diazoxide also failed to suppress EGP in diabetic rats. These results suggest that suppression of EGP by central KATP channel activation may be lost in type 2 diabetes. Restoration of central regulation of glucose metabolism could be a promising therapeutic target to reduce hyperglycemia in type 2 diabetes.

Assessing a low-cost accelerometer-based technique to estimate spatial gait parameters of lower-limb prosthesis users.

BACKGROUND AND AIM: Inexpensive methods for characterizing lower-limb prosthetic gait allow clinicians to monitor gait quality. This study assessed an established method for estimating step length using a low-cost accelerometer to estimate distance walked in lower-limb prosthesis users and explore the use of subject-specific correction factors. TECHNIQUE: A three-axis accelerometer was attached to participants using straps. Validity and test-retest reliability of step length was assessed in able-bodied individuals using a motion capture system. Validity of distance walked was assessed with lower-limb prosthesis users. A regression equation was developed for prosthesis users to estimate a correction factor that minimized error. DISCUSSION: The system demonstrated excellent reliability and minimal mean error for both participant groups, but subject-specific correction factors did not provide substantial benefit. Estimate variability was high, suggesting the need for further refinement. Estimating distance walked and step length from low-cost accelerometers may be a valid, clinically accessible method for characterizing prosthetic gait. CLINICAL RELEVANCE: The use of a low-cost accelerometer may provide valid means for estimating step length and distance walked of lower-limb prosthesis users in a clinical environment for monitoring patient outcomes.

Different imaging characteristics of concurrent pituitary adenomas in a patient with Cushing's disease.

We report a patient with Cushing's disease (CD) and two pituitary adenomas that demonstrated different imaging characteristics and therefore suggest an alternative imaging strategy for these patients. A 42-year-old woman presented with signs and symptoms of CD. Biochemical evaluation confirmed hypercortisolemia and suggested CD. On pituitary MRI with spoiled gradient recalled acquisition in the steady-state and T1-weighted spin echo protocols, a 5mm hypoenhancing region typical for a pituitary adenoma was identified on the left. However, after surgical resection the patient remained hypercortisolemic and pathology revealed a non-functional adenoma. At early repeat surgical exploration a 10mm adenoma was found in the right side of the gland. Postoperatively the patient became hypocortisolemic and pathology demonstrated an adrenocorticotropic hormone (ACTH)-staining adenoma. On review of the initial MRI this tumor corresponded to a region of contrast retention best visualized on delayed fluid attenuated inversion recovery (FLAIR) imaging. While the incidentaloma in this case demonstrated classical imaging characteristics of a pituitary adenoma the larger ACTH-secreting tumor was best appreciated by contrast retention. This suggests a role for delayed postcontrast FLAIR imaging in the preoperative evaluation of CD. ACTH-secreting tumors causing CD cause significant morbidity. Due to their small size, a pituitary adenoma is frequently not identified on imaging despite endocrinologic testing suggesting CD. Regardless of improvements in MRI, many tumors are only identified at surgical exploration.

Insulin sensitizing and anti-inflammatory effects of thiazolidinediones are heightened in obese patients.

OBJECTIVE: The American Diabetes Association has called for further research on how patients' demographics should determine drug choices for individuals with type 2 diabetes mellitus (T2DM). Here, using in-depth physiology studies, we investigate whether obese patients with T2DM are likely to benefit from thiazolidinediones, medications with a known adverse effect of weight gain. MATERIALS AND METHODS: Eleven obese and 7 nonobese individuals with T2DM participated in this randomized, placebo-controlled, double-blind, crossover study. Each subject underwent a pair of "stepped" pancreatic clamp studies with subcutaneous adipose tissue biopsies after 21 days of pioglitazone (45 mg) or placebo. RESULTS: Obese subjects demonstrated significant decreases in insulin resistance and many adipose inflammatory parameters with pioglitazone relative to placebo. Specifically, significant improvements in glucose infusion rates, suppression of hepatic glucose production, and whole fat expression of certain inflammatory markers (IL-6, IL-1B, and inducible nitric oxide synthase) were observed in the obese subjects but not in the nonobese subjects. Additionally, adipose tissue from the obese subjects demonstrated reduced infiltration of macrophages, dendritic cells, and neutrophils as well as increased expression of factors associated with fat "browning" (peroxisome proliferator-activated receptor gamma coactivator-1α and uncoupling protein-1). CONCLUSIONS: These findings support the efficacy of pioglitazone to improve insulin resistance and reduce adipose tissue inflammation in obese patients with T2DM.

Multiple intestinal intussusceptions as a complication of severe hyperglycemia in a patient with diabetic ketoacidosis.

Intussusception in adults is a rare phenomenon, occurring in approximately 1 in 30,000 hospital admissions annually. When it does occur, the majority of cases involve an organic lesion serving as a lead point for intussusception, such as tumors or postoperative adhesions. In a small percentage of cases, a lead point is not found, and intussusception is thought to be idiopathic or secondary to a disease process contributing to dysrhythmic peristalsis of the gastrointestinal tract. A few cases of functional intussusception have been reported as being secondary to severe hyperglycemia and metabolic derangements, including metabolic acidosis and hyperkalemia, by causing impaired gastrointestinal motility. We present a case of a 23-year-old Caucasian male who presented with severe hyperglycemia and diabetic ketoacidosis. Imaging of the abdomen revealed three intussusceptions involving the small intestine, which were easily reduced manually during exploratory laparotomy.

Role of teriparatide in accelerating metatarsal stress fracture healing: a case series and review of literature.

Bone fractures are one of the leading causes of emergency room visits worldwide, with approximately 8 million bony fractures occurring annually in the US alone. Although the majority of fractures do not cause significant long-term morbidity and mortality, approximately 10% of these fractures result in impaired fracture healing, drastically affecting quality of life in affected patients. By increasing bone formation, teriparatide, an anabolic agent used in the treatment of postmenopausal osteoporosis, has shown promise in accelerating the rate of fracture healing. We present two patients with impaired healing of metatarsal fractures who were subsequently treated with teriparatide. Both patients experienced successful bony union of the fracture after the use of teriparatide. These findings suggest that teriparatide may be useful in the clinical setting for the acceleration of fracture healing, especially in patients who are at risk for impaired fracture healing.

Isolated pancreatic tuberculosis mimicking malignancy in an immunocompetent host.

Despite the high prevalence of tuberculosis (TB) worldwide, pancreatic TB is rare. When present, pancreatic TB is frequently associated with miliary TB, often in immunocompromised hosts. Pancreatic TB may present as a pancreatic abscess, acute or chronic pancreatitis, and cystic or solid pancreatic masses. We present a case of an immunocompetent patient who presented with two discrete pancreatic masses and was subsequently diagnosed with isolated pancreatic TB. This case suggests that clinicians should have a heightened suspicion of pancreatic TB when faced with discrete pancreatic lesions, especially in patients from areas where the infection is endemic. Such recognition may lead to appropriate diagnostic testing, and possible resolution of pancreatic lesions with antituberculin therapy.

Direct liver invasion from a gastric adenocarcinoma as an initial presentation of extranodal tumor spread.

Gastric cancer often carries a poor prognosis, with an estimated 740,000 deaths from the malignancy occurring yearly worldwide (Dicken et al., 2005). The mortality of disease is largely dependent on the extent of tumor spread, as gastric cancer has a predilection to metastasize to other visceral secondaries via hematogenous and lymphatic dissemination. Direct invasion of a gastric adenocarcinoma to adjacent organs secondary to gastric wall perforation does occur; however, it is often present in the setting of advanced disease. Rarely does direct tumor invasion to adjacent organs from a gastric adenocarcinoma present as the initial manifestation of extranodal tumor spread. We present a case of a 40-year-old male with direct tumor extension to the liver as an initial presentation of extranodal tumor spread from a gastric adenocarcinoma. Clinicians should be aware of such an occurrence, as treatment modalities in direct liver extension from a gastric adenocarcinoma vary and may be directed towards palliation rather than curative intent.

Acute pancreatitis induced by methimazole therapy.

Among the causative factors for acute pancreatitis, adverse drug reactions are considered to be rare. The diagnosis of drug-induced pancreatitis (DIP) is challenging to establish, and is often underestimated because of the difficulties in determining the causative agent and the need for a retrospective re-evaluation of the suspected agent. We present the case of an 80-year-old woman who presented with complaints of abdominal pain. Her medications included methimazole (MMI) which she had been on for the past 3 months. Computed tomography of her abdomen showed peripancreatic fat stranding with trace amount of surrounding fluid, along with amylase and lipase levels suggestive of acute pancreatitis. In the absence of classical risk factors for acute pancreatitis, a diagnosis of DIP secondary to MMI use was made. Withdrawal of the drug from her medication regimen was accompanied by relief of symptoms and resolution of clinical evidence of pancreatitis. The aim of this paper is to report only the fourth case of MMI-induced pancreatitis in the published literature, and to illustrate the significance of an appropriate and timely diagnosis of DIP.

Lower extremity cutaneous lesions as the initial presentation of metastatic adenocarcinoma of the colon.

Cutaneous metastases from colorectal cancers are rare and are usually present on the abdominal wall or previous surgical incision sites. Remote cutaneous lesions have been reported, however, often occur in the setting of widespread metastatic disease including other visceral secondaries. We present a case of lower extremity cutaneous metastases as the first sign of metastatic disease in a patient with adenocarcinoma of the colon. This case illustrates that new skin lesions may be the initial presentation of metastatic disease in a patient with a history of cancer.

Pseudohypoparathyroidism type Ia manifesting as intractable epilepsy in a 23-year-old female.

Pseudohypoparathyroidism is a rare disorder of calcium metabolism that involves target organ resistance to the action of the parathyroid hormone. As a result, calcium levels may become dangerously low, sometimes leading to seizures and other symptoms. We present a case of a 23-year-old Somalian female on antiepileptic therapy presenting with intractable epilepsy. She was subsequently found to have pseudohypoparathyroidism type Ia. She had multiple reasons accounting for loss of seizure control, including worsening hypocalcemia from resistance to the parathyroid hormone; vitamin D deficiency, which could have resulted from lack of exposure to direct sunlight and her antiepileptic medication; and extensive calcium deposition in the brain due to pseudohypoparathyroidism. The patient was stabilized with intravenous therapy and oral calcium, vitamin D, and calcitriol. Her antiepileptic therapy was changed to a medication that did not interfere with vitamin D metabolism or contribute to worsening hypocalcemia.