Jennifer Wyckoff

Under-recognised paradox of neuropathy from rapid glycaemic control

Insulin induced neuropathy has been reported previously in people with diabetes treated with insulin, and subsequently reported in patients with insulinomas. However, neuropathy caused by rapid glycaemic control in patients with poorly controlled diabetes with chronic hyperglycaemia is not a widely recognised entity among clinicians worldwide. It is expected that this phenomenon of paradoxical complication of neuropathy in the face of drastic decreases in glycosylated haemoglobin concentrations will assume greater importance with clinicians achieving glycaemic targets at a faster pace than before.

The association of circulating angiogenic factors and HbA1c with the risk of preeclampsia in women with preexisting diabetes

Objective: To assess whether glycemic control, soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) were associated with the development of preeclampsia (PE) or gestational hypertension (GHTN) in women with preexisting diabetes. Methods: Maternal circulating angiogenic factors (sFlt1 and PlGF) measured on automated platform were studied at four time points during pregnancy in women with diabetes (N = 159) and reported as multiples of the median (MOM) of sFlt1/PlGF ratio (median, 25th–75th percentile) noted in non-diabetic non-hypertensive control pregnant population (N = 139). Diagnosis of PE or GHTN was determined by review of de-identified clinical data. Results: PE developed in 12% (N = 19) and GHTN developed in 23% (N = 37) of the women with diabetes. Among diabetic women without PE or GHTN, median sFlt1/PlGF levels at 35–40 weeks was threefold higher than in non-diabetic controls [MOM 3.21(1.19–7.24), p = 0.0001]. Diabetic women who subsequently developed PE had even greater alterations in sFlt1/PlGF ratio during the third trimester [MOM for PE at 27–34 weeks 15.18 (2.37–26.86), at 35–40 weeks 8.61(1.20–18.27), p ≤ 0.01 for both windows compared to non-diabetic controls]. Women with diabetes who subsequently developed GHTN also had significant alterations in angiogenic factors during third trimester; however, these findings were less striking. Among women with diabetes, glycosylated hemoglobin (HbA1c) during the first trimester was higher in subjects who subsequently developed PE (7.7 vs 6.7%, p = 0.0001 for diabetic PE vs diabetic non-PE). Conclusions: Women with diabetes had a markedly altered anti-angiogenic state late in pregnancy that was further exacerbated in subjects who developed PE. Altered angiogenic factors may be one mechanism for the increased risk of PE in this population. Increased HbA1c in the first trimester of pregnancies in women with diabetes was strongly associated with subsequent PE.

Using Oral Agents to Manage Gestational Diabetes: What Have We Learned?

Insulin has been the mainstay of treatment of diabetes during pregnancy for decades. Although glyburide and metformin are classified as category B during pregnancy, recent research has suggested that these oral agents alone or in conjunction with insulin may be safe for the treatment of gestational diabetes (GDM). This paper summarizes the data on the use of glyburide and metformin for treatment of GDM.

Moyamoya syndrome causing stroke in young women with type 1 diabetes

CONTEXT Moyamoya syndrome is an idiopathic brain vasculopathy characterized by stenosis of major intracranial arteries. It often presents in patients with type 1 diabetes or thyroid disease and may have an autoimmune etiology. Moyamoya-related stroke poses a diagnostic challenge as initial symptoms and deficits vary greatly from classic ischemic stroke to encephalopathy, psychiatric, or seizure disorder. CASE DESCRIPTION We report 4 patients with type 1 diabetes and other autoimmune diseases who developed moyamoya-related stroke at a young age. Despite having long-term diabetes, these patients exhibited no evidence of dyslipidemia or other typical risk factors for atherosclerosis which might contribute to premature stroke. Three of the four patients underwent revascularization surgery while one patient received conservative management. All patients had improved neurologic function after treatment, some with residual deficits. CONCLUSION We highlight the importance of recognizing moyamoya syndrome in patients with pre-existing autoimmune diseases such as type 1 diabetes, as prompt diagnosis and treatment can have major impact on patient outcome and quality of life.

Acute dysautonomia: a rare manifestation of diabetic autonomic neuropathy masquerading as pheochromocytoma

Dear Editor, Diabetes mellitus is one of the commonest causes of autonomic neuropathy. Rarely, diabetic autonomic neuropathy (DAN) may present as acute dysautonomia with autonomic crisis, which includes paroxysmal spells typical of pheochromocytomas. An extensive search of the medical literature shows a distinct paucity of this form of diabetic autonomic dysfunction. We report the following patient, in whom DAN mimicked a pheochromocytoma. A 24-year-old white female was diagnosed at age 13 with type 1 diabetes mellitus. Her family history was only significant for a maternal grandfather with type 2 diabetes. For the past 8 years, her HbA1c ranged between 10.2 and 12.4%. She remained well without chronic diabetic complications until 6 months prior to presentation when she developed symmetrical paresthesia of her distal extremities relieved by gabapentin. She then suffered frequent hypoglycemia from self-imposed tight glycemic control to reduce further complications and noticed a lack of hypoglycemia awareness. Her HbA1c was 6.5% at presentation, when she experienced episodic headaches associated with palpitations, hypertension, orthostatic dizziness, and diaphoresis unrelated to hypoglycemia. During these paroxysms, her capillary blood glucose ranged between 5 and 10 mM. She had not abused alcohol, amphetamines, cocaine, or decongestants and never had panic disorder or diencephalic seizures. Physical examination revealed supine hypertension with blood pressure (BP) of 170/120 mmHg with mild orthostasis associated with resting tachycardia of 130 per minute. There was peripheral neuropathy of her lower limbs. Her thyroid function test was normal. In view of persistent tachycardia, severe hypertension with labile BP unrelated to hypoglycemia, plasma catecholamines were screened to evaluate for a pheochromocytoma. Despite an elevated baseline plasma norepinephrine level of 1219 pM (NR: 112-658), a normal clonidine suppression test with final plasma norepinephrine of 200 pM excluded pheochromocytoma. Autonomic function testing confirmed resting tachycardia, impaired heart rate variability, and orthostasis consistent with autonomic neuropathy with greater parasympathetic than sympathetic dysfunction. DAN is a chronic autonomic neuropathy, in which combined sympathetic and parasympathetic failure occur over a wide spectrum (Low and McLeod, 1997). At one extreme is panautonomic neuropathy characterized by widespread and severe sympathetic and parasympathetic failure. Acute dysautonomia complicated by autonomic storm forms the other end of the spectrum. Our patient illustrates an uncommon scenario, in which autonomic overactivity predominates over autonomic failure. In dysautonomia, both autonomic overactivity and autonomic failure are present and often coexist in a single patient, with varying degrees of expression at any given time (Low and McLeod, 1997). In particular, she had pronounced sympathetic overactivity manifested by hypertension associated with the triad of headaches, palpitations, and diaphoresis indistinguishable from pheochromocytomas. However, the suppressible hypercatecholaminemia implied that her situation was a case of ‘pseudo-pheochromocytoma.’ Importantly, hypoglycemia itself can evoke adrenergic symptoms mimicking pheochromocytoma. However, because she had no demonstrable hypoglycemia during her ‘spells’ and was subsequently proven to have autonomic neuropathy by autonomic function tests, we hypothesized that her paroxysms were due to acute dysautonomia. Thus far, ‘diabetic dysautonomia’ is an extremely rare condition in the medical literature and deserves an addition to our existing knowledge of DAN. Unlike acute autonomic neuropathy, chronic autonomic neuropathy including DAN shows little tendency Address correspondence to: Melvin Khee Shing Leow, Tan Tock Seng Hospital, Department of Endocrinology, Division of Medicine, 11 Jalan Tan Tock Seng, Singapore 308433. Tel: þ65-62566011; Fax: þ65-63577588; E-mail: mleowsj@massmed.org Journal of the Peripheral Nervous System 10:382–383 (2005)

Preconception Care for Women with Diabetes Mellitus

Established preexisting diabetes affects over 1% of pregnancies, and that number is expected to rise. Hyperglycemia during the first few weeks of pregnancy can result in congenital malformations or miscarriage. Preexisting diabetes increases the risk of developing both fetal and maternal complications in pregnancy; some of which can be devastating. Through careful attention to contraception, preconception counseling and preconception medical care, many of these complications can be avoided. Preconception care (PCC) programs have been shown to be efficacious at reducing complications and perinatal mortality as well as cost effective. Wider adoption of PCC programs is needed.