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Iodine Research

Resource Network of The Iodine Movement

Diabetes

Orthoiodosupplementation in a Primary Care Practice
Flechas JD.

In the Type 1 diabetics that we have been following we have noted that if C-peptide is measurable, this
would suggest that the individual is making their own insulin. I have been able to help this group of
patients to get off insulin or to greatly reduce the amount they need for good glucose control with Iodoral
at 4 tablets/day (50 mg). If C-peptide is absent, then we feel there is no insulin being produced and we
have not been able to help this particular group of patients to get off their insulin. We have been able to
help these patients lower the total amount of insulin needed to control their glucose.

It was while treating a large 320-pound woman with insulin dependent diabetes that we learned a
valuable lesson regarding the role of iodine in hormone receptor function. This woman had come in via
the emergency room with a very high random blood sugar of 1,380 mg/dl. She was then started on
insulin during her hospitalization and was instructed on the use of a home glucometer. She was to use
her glucometer two times per day. Two weeks later on her return office visit for a checkup of her insulin
dependent diabetes she was informed that during her hospital physical examination she was noted to
have FBD. She was recommended to start on 50 mg ofiodine(4 tablets) at that time. One week later she
called us requesting to lower the level of insulin due to having problems with hypoglycemia. She was told
to continue to drop her insulin levels as long as she was experiencing hypoglycemia and to monitor her
blood sugars carefully with her glucometer. Four weeks later during an office visit her glucometer was
downloaded to my office computer, which showed her to have an average random blood sugar of 98. I
praised the patient for her diligent efforts to control her diet and her good work at keeping her sugars
under control with the insulin. She then informed me that she had come off her insulin three weeks
earlier and had not been taking any medications to lower her blood sugar. When asked what she felt the
big change was, she felt that her diabetes was under better control due to the use of iodine. Two years
later and 70 pounds lighter this patient continues to have excellent glucose control on iodine 50 mg per
day. We since have done a study of twelve diabetics and in six cases we were able to wean all of these
patients off of medications for their diabetes and were able to maintain a hemoglobin A1C of less than
5.8 with the average random blood sugar of less than 100. To this date these patients continue to have
excellent control of their Type II diabetes. The range of daily iodine intake was from 50 mg to 100 mg per
day. All diabetic patients were able to lower the total amount of medications necessary to control their
diabetes. Two of the twelve patients were controlled with the use of iodine plus one medication. Two
patients have control of diabetes with iodine plus two medications. One patient had control of her
diabetes with three medications plus iodine 50 mg. The one insulin dependent diabetic was able to
reduce the intake of Lantus insulin from 98 units to 44 units per day within a period of a few weeks.


Thyroid function, morphology and autoimmunity in young patients with insulin-dependent diabetes
mellitus.
Hansen D, Bennedbaek FN, Hansen LK, Hoier-Madsen M, Jacobsen BB, Hegedus L.
Eur J Endocrinol. 1999 Jun;140(6):512-8.

OBJECTIVE: An association between insulin-dependent diabetes mellitus (IDDM) and autoimmune thyroid
disease is well recognized. We have studied the prevalence of thyroid dysfunction, autoimmunity and
morphological abnormalities by ultrasonography in young diabetics.

SUBJECTS AND METHODS: Among young IDDM patients less than 18 years old and living in the county of
Funen, Denmark, 105 of 116 eligible patients participated. They were compared with 105 healthy children
matched for sex and age. Routine thyroid function parameters (thyroxine (T4), tri-iodothyronine (T3), T3
resin uptake and TSH) and thyroid autoantibodies (anti-thyroid peroxidase, TPOab, and thyroglobulin
antibodies, Tgab) were measured. Thyroid size and morphology were determined by ultrasonography.

RESULTS: Two of the diabetics had previously diagnosed hypothyroidism and three new cases of
subclinical hypothyroidism were found. There were no significant differences in thyroid function
variables or thyroid volume between diabetics and controls. Thyroid volume correlated significantly with
age and weight in both groups. Among diabetics, 17 had thyroid autoantibodies (13 with TPOab, 14 with
Tgab and 10 with both) compared with 2 children in the control group (P<0.001). Forty-four with IDDM as
opposed to 11 of the controls (P<0.001) had morphological abnormalities at ultrasonography. Most of
them had various degrees of hypoechogenicity thought to be a marker of thyroid autoimmunity. Among
the 17 diabetics with autoantibodies, 10 had morphological abnormalities at ultrasonography.

CONCLUSIONS: A high proportion of young IDDM patients without any clinical signs of thyroid disease
have markers of thyroid autoimmunity. Many have thyroid autoantibodies, but even more have
abnormalities by thyroid ultrasonography.

High prevalence of thyroid autoantibodies at diagnosis of insulin-dependent diabetes mellitus in Swedish
children.
Lindberg B, Ericsson UB, Ljung R, Ivarsson SA.
J Lab Clin Med. 1997 Dec;130(6):585-9.
[abstract only]

The prevalence of thyroglobulin autoantibodies and that of thyroid peroxidase autoantibodies were
studied in serum samples from 52 children with insulin-dependent diabetes mellitus, sampled at
diagnosis and before the start of insulin treatment, with 386 non-diabetic schoolchildren (11 to 13 years
of age) serving as control subjects. Using exactly the same sensitive solid-phase immunosorbent
radioassay for both thyroid autoantibodies, with comparable sensitivity, we found the prevalences of
both autoantibodies to be higher in the insulin-dependent diabetes mellitus group than in the control
group, the difference being most pronounced for thyroid peroxidase autoantibodies. Thyroglobulin
autoantibodies were positive in 33% of the diabetics versus 14% in the control group (p = 0.002), and
thyroid peroxidase autoantibodies were positive in 38% versus 6% (p = 0.0001). The high prevalence of
thyroid autoantibodies already at diagnosis stresses the importance of early screening for thyroid
disease in patients with insulin-dependent diabetes mellitus.

Iodine status, thyroid function, thyroid volume and thyroid autoimmunity in patients with type 1 diabetes
mellitus in an iodine-replete area.
Okten A, Akcay S, Cakir M, Girisken I, Kosucu P, Deger O.
Diabetes Metab. 2006 Sep;32(4):323-9.
[abstract only]

OBJECTIVE: To analyze the prevalence and clinical significance of thyroid autoimmunity, thyroid volume
and iodine status in patients with type 1 diabetes mellitus compared with age and sex matched healthy
controls, in an iodine-deficiency improved area.

METHOD: Fifty-eight patients with type 1 DM, 30 female and 28 male, who attended the pediatric
endocrinology clinic of Karadeniz Technical University Hospital were included into the study. They were
compared with 58 healthy children matched for sex and age. Routine thyroid function parameters,
thyroid autoantibodies (TPOAb, TGAb and TRAb) and urinary iodine excretion were measured and thyroid
volume was determined by ultrasonography (US).

RESULTS: Twenty-six patients (44.8%) in diabetic patients and 20 subjects (34.5%) in the control group
had thyroid autoantibody positivity. TPOAb and TGAb positivity were significantly high in diabetic patients
(P=0.01 and P=0.032, respectively). Thyroid US revealed a thyroid volume of 6.6+/-3.5 ml (median 6.4 ml,
range 1.117.2 ml) in the diabetic patients compared with 3.7+/-2 ml (median 3.1 ml, range 0.8-8.6 ml) in
the control group (P=0.0001). Median urinary iodine levels of both groups were clearly above the
threshold level for iodine deficiency, but 26 patients with type 1 DM (44.8%) and 16 controls (27.5%) had
urinary iodine excretion below 100 microg/L, and 21 (36.2%) of diabetic patients and two subjects (3.4%)
of the control group were consistent with severe iodine deficiency. No significant differences were
noted in diabetic patients in terms of age, duration and metabolic control of the disease and thyroid
volume when compared according to the autoantibody presence. Additionally, there were no significant
differences between the iodine deficient and iodine sufficient diabetic patients in terms of age, sex,
duration of disease, HbA1c, thyroid hormones and thyroid volumes. Thyroid autoimmunity was lower in
patients with iodine deficiency (38.4% vs. 50%), but not statistically significant.

CONCLUSION: We found that type 1 DM patients had larger thyroid volume compared with healthy control
groups, and a large portion of them had the markers of autoimmune thyroid disease and iodine
deficiency. Surprisingly, we found that a large portion of the healthy children had TRAb positivity. We
proposed that TRAb must be considered in community surveys or prevalence studies of autoimmune
thyroid disorders in iodine-replete areas. Additionally, prospective longitudinal studies are needed to
determine the clinical significance of TRAb positivity in diabetic patients.

Screening for associated autoimmunity in type 1 diabetes mellitus with respect to diabetes control.
Prazny M, Skrha J, Limanova Z, Vanickova Z, Hilgertova J, Prazna J, Jaresova M, Striz I.
Physiol Res. 2005;54(1):41-8.

As an autoimmune disease, type 1 diabetes mellitus (DM) can be associated with other autoimmune
disorders. The aim of this study was to detect subclinically associated autoimmune thyroid disease,
coeliac disease, and Addison's disease. The presence of autoantibodies was evaluated with special
regard to the control of diabetes and to the clinical status of the patient. Fifty-one type 1 diabetic patients
(22 men, 29 women, mean age 37+/-11 years, mean duration of diabetes 16+/-13 years) were included
into this study. Specific antibodies to islet antigens--glutamic acid decarboxylase (GAD65), protein
thyrosine phosphatase IA-2alpha, and to thyroid autoantigens--thyroid microsomal peroxidase (TPO) and
thyroglobulin (TG) and also thyroid stimulating hormone (TSH) were measured by RIA. Autoantigens of
the small intestine--tissue transglutaminase autoantibodies (ATTG), IgA and IgG antibodies to gliadin
(AGA-IgA, AGA-IgG) were evaluated by ELISA. Endomysial autoantibodies (EMA) and adrenal cortex
antibodies (ACA) were detected by indirect immunofluorescence microscopy. Eleven new cases of
thyreopathy (22 % of patients) were detected by the assessment of thyroid autoantibodies and TSH. Two
new cases of thyreotoxicosis were diagnosed during the study. Coeliac disease was diagnosed in at
least two cases. Addison's disease was not diagnosed, although the ACA were positive in two patients.
No influence of single or combined autoantibody positivity on the control of diabetes was found if normal
organ function was preserved. In both patients with thyreotoxicosis the control of diabetes was
worsened and improved after treatment. The screening of autoantibodies in type 1 diabetic patients
could reveal subclinical cases of AITD or coeliac disease. Subclinical forms of these disorders have no
influence on diabetes control. However, impaired organ function may be associated with the worsened
control of diabetes as we demonstrated on two newly diagnosed cases of thyreotoxicosis. We suggest
the need for the follow-up of patients with positive autoantibodies because further deterioration of the
respective organs can be expected.


[Thyroid gland ultrasound and urinary iodine excretion in children and adolescents with type I diabetes
mellitus]
Steiss JO, Otten A, Graef V, Klingmuller V.
Klin Padiatr. 1996 Nov-Dec;208(6):327-33. German.
[abstract only]

BACKGROUND: Date, studies on thyroid volume and urinary iodide excretion in patients with diabetes
mellitus are not available. Sonographically determined parameters of the thyroid size are correlated to
other anthropometrous data and the urinary iodide excretion is correlated to glucosuria, the HbA1c
value and the diabetes duration.

METHOD: In this prospective study we evaluated sonographically the thyroid volume in 107 patients with
type I diabetes mellitus and 112 healthy children. The urinary iodide excretion was measured
photometrically by using a modified ceric ion arsenious acid method for spontaneous urinary specimen
and if available for the 24 h collected urin.

RESULTS: The thyroid volume depended on site and age. A positive correlation of the thyroid volume and
age, body weight and height, could be demonstrated. Referring to reference data a goitre prevalence of
30% in juvenile patients with diabetes mellitus type I was detected. Interestingly, juvenile type I diabetics
presented with an average urinary iodide excretion of 183.0 micrograms iodide/g creatinine. Even the
urinary iodide excretion of 162.5 micrograms iodide confirmed this increased level. The urinary iodide
excretion in 24 hours correlated with glucosuria and the HbA1c level. The healthy children presented
with an average urinary iodide excretion of 42.6 micrograms iodide/g creatinine. The mean value was
clearly below the WHO recommendation of 150-300 micrograms iodide/g creatinine. Only 2.8% of the
healthy children examined exceeded the lower limit of this range.

CONCLUSION: In addition to the existing distinct under supply of iodide we assume an increased urinary
iodide excretion in context with the osmotic diuresis in juvenile diabetics. Contrary to current opinion,
that these data are correlated to the daily intake of iodide, which was calculated from urinary excretion
rate, this thesis could not be affirmed for juvenile diabetics. Therefore it seems reasonable to frequently
control thyroid volume and thyroid function in children and adolescents with diabetes mellitus.


Thyroid gland diseases in adult patients with diabetes mellitus.
Vondra K, Vrbikova J, Dvorakova K.
Minerva Endocrinol. 2005 Dec;30(4):217-36. Review.
[abstract only]

This review concerns the relation between most frequent thyroid gland diseases and diabetes mellitus
in adult patients. Special attention is paid to autoimmune thyroiditis, Graves' disease, thyroid
autoimmunity in pregnant diabetic women, and iodine metabolism. We focused on mechanisms leading
to coexistence of both endocrine disorders, and on distinctions in the prevalence, diagnosis, clinical
course and treatment of thyroid diseases in diabetic patients. The prevalence of thyroid diseases in
diabetic patients is 2-3 times higher than in nondiabetic subjects; it raises with age, and is strongly
influenced by female gender and autoimmune diabetes. Clinical relevance of thyroid diseases, especially
in diabetic patients, significantly increases if it is associated with deteriorated function, which always
cause a number problems with metabolic compensation of diabetes. Most serious consequences are
increased frequency of hypoglycaemia in hypothyroidism and development of potentially life-threatening
ketoacidosis in thyrotoxicosis. In spite of that, little attention is paid to the diagnosis of thyroid diseases
in diabetics, as they are diagnosed in only about half of the patients. At the end, we provide
recommendations for the thyroid disease screening and diagnosis in patients with diabetes mellitus
based on our experience.


Alterations of antioxidant tissue defense enzymes and related metabolic parameters in
streptozotocin-diabetic rats--effects of iodine treatment.
Winkler R, Moser M.
Wien Klin Wochenschr. 1992;104(14):409-13.
[abstract only]

This study reports on the effect of streptozotocin (STZ) induced diabetes on water soluble-SH and -SS,
as well as on hepatic glutathione peroxidase (GSH-Px), catalase and superoxide dismutase (SOD)
activity and on malondialdehyde (MDA) content. In addition, we determined serum concentrations of
glucose, cholesterol, triglycerides and thyroxine, and thyroid weight. To elucidate the possible impact of
exogenous iodine on impaired free radical tissue defense mechanisms STZ-diabetic rats were exposed
to iodine brine providing for a daily iodide uptake of about 300 micrograms/kg body weight.
STZ-exposure caused a decline in thyroid weight (p less than 0.01) and in total serum thyroxine (p less
than 0.001), as well as a fall in hepatic catalase (CAT) activity (p less than 0.01) versus control group.
Impairment of catalase activity was related to serum glucose level (r = -0.569, p less than 0.01), while
hepatic MDA was positively related to serum glucose (r = + 0.5, p less than 0.01). No protective effects of
iodine brine were seen with regard to impairment by STZ of antioxidant enzyme status. We conclude
that impairment by STZ of antioxidant enzymes may contribute to STZ-dependent experimental diabetes.


The effect of halides (NaCl and NaI) on in vitro pancreatic elastase activity.
Winkler RH.
Connect Tissue Res. 1978;6(2):89-92.
[abstract only]

The effect of I- and Cl- on the enzymatic degradation of elastin pancreatic elastase has been studied. At
low halide concentrations both ions show a marked stimulation of elastolysis, I- being significantly more
effective than Cl-. Kinetic plots of enzyme activity indicate that anions enhance the susceptibility of the
substrate to enzymatic and non-enzymatic degradation. If the halide concentration is raised inhibition of
elastolysis occurs starting at 30 mM NaCl and 300 mM NaI. This inhibitory effect is explained by a direct
attack of the halides leading to increasing destabilization and inactivation of the enzyme.
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